阿茲海默症(AD)為一種常見的與年齡相關的神經退化性失智症。其病理特徴包含在大腦中存在澱粉樣蛋白-β (Aβ)斑塊和神經纖維纏結(NFTs)的慢性累積。NFTs是由成對螺旋絲(PHF)在神經元內累積而成，而PHF主要是異常過度磷酸化Tau蛋白組成，會誘導一系列毒性事件，最終導致神經元變性和損傷。腦原性神經營養因子(BDNF)為一種神經營養因子。BDNF與其特異性受體原肌球蛋白相關激酶B (TRKB)結合後，導致TRKB二聚化和活化，隨後活化下游訊號，影響cAMP反應元件結合蛋白1 (CREB)在內的蛋白，來促進神經元存活和增加神經可塑性。證據顯示，在AD患者的大腦中BDNF和TRKB的表達量降低，因此增強TRKB訊號被認為是有希望的治療策略。本研究使用表達ΔK280 TauRD-DsRed促Tau錯誤折疊聚集的人類神經母細胞瘤SH-SY5Y細胞，評估8種化合物抑制Tau錯誤折疊的情形。檢測的化合物中，香豆素衍生物ZN-015和喹啉衍生物VB-030和VB-037可減少細胞內ΔK280 TauRD聚集，並促進神經突生長。通過抑制細菌衍生的ΔK280 TauRD-His在生化分析中的聚集，ZN-015、VB-030和VB-037顯示出化學伴侶活性。此三者雖皆不具DPPH自由基捕捉能力，但ZN-015具氧自由基吸收能力。另外，ZN015、VB-030和VB-037抑制了凋亡蛋白酶-1 (Caspase 1)及/或乙醯膽鹼酯酶(AChE)活性。進一步的TRKB訊息傳遞路徑分析顯示，處理ZN-015、VB-030、VB-037後，細胞內p-TRKB (Y516)、p-TRKB (Y817)、p-AKT (S473)、p-ERK (T202/Y204)、p-RSK (S380)、p-CaMKII (T286)、p-CREB (S133)、BDNF、BCL2蛋白表現顯著增加，並伴隨著凋亡調節蛋白BAX的顯著降低。以TRKB的干擾性核糖核酸(RNAi)靜默TRKB基因表現後，可抑制ZN-015、VB-030、VB-037的促進神經突生長。色氨酸螢光猝滅分析(Tryptophan fluorescence quenching assay)顯示，ZN-015、VB-030、VB-037與畢赤酵母表達的TRKB胞外結構域(TRKB-ECD)直接相互作用，支持其透過TRKB訊號發揮作用。這些化合物作為TRKB促效劑的研究，能為AD提供新的治療策略。

Alzheimer’s disease (AD) is a degenerative brain disease and the most common form of age-related dementia. It is well known that patients with AD have a progressive deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. NFTs are formed by intraneuronal accumulation of paired helical filaments composed of abnormally hyperphosphorylated Tau protein, which induce a series of toxic events to result in neurodegeneration and neuronal loss. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor. Binding of BDNF to tropomyosin-related kinase B (TRKB) receptor leads to its dimerization and activation and subsequently induces the activation of several intracellular signaling cascades, which ultimately phosphorylates cAMP responsive element binding protein 1 (CREB) and promotes neuronal survival and neuroplasticity. Reduced BDNF and TRKB expression levels have been found in brains of AD patients. Therefore, enhancement of TRKB signaling is a promising AD treatment strategy. In this study, eight compounds were evaluated for inhibiting Tau misfolding in human neuroblastoma SH-SY5Y cells expressing pro-aggregant ΔK280 TauRD-DsRed. Among them, coumarin derivative ZN015 and quinoline derivatives VB-030 and VB-037 reduced ΔK280 TauRD aggregation and promoted neurite outgrowth in these cells. By inhibiting bacterial-derived ΔK280 TauRD-His aggregation in biochemical assay, ZN015, VB-030 and VB-037 displayed chemical chaperone activity. Although these three have no DPPH free radical scavenging ability, but ZN-015 has oxygen free radical antioxidant activity. In addition, ZN015, VB-030 and VB-037 inhibited the caspase 1 and/or acetylcholinesterase (AChE) activity. Studies of TRKB signaling revealed that treatment of ZN-015, VB-030 and VB-037 significantly increased the expression of p-TRKB (Y516), p-TRKB (Y817), p-AKT (S473), p-ERK (T202/Y204), p-RSK (S380), p-CaMKII (T286), p-CREB (S133), BDNF and BCL2, accompanying with reduced BAX expression in ΔK280 TauRD-DsRed cells. Furthermore, the neurite outgrowth promotion effect of ZN-015, VB-030 and VB-037 was counteracted by knockdown of TRKB using RNA interference (RNAi). Tryptophan fluorescence quenching analysis showed that ZN-015, VB-030, and VB-037 interact directly with Pichia pastoris-expressed TRKB extracellular domain (TRKB-ECD), supporting its role through TRKB signaling. The study of these compounds as TRKB agonists may provide new treatment strategies for AD.

陳炫江. (2013). 以tau聚集為目標的阿茲海默氏症治療策略. 國立臺灣師範大學生命科學系碩士論文.
(2021) 2021 Alzheimer’s disease facts and figures. Alzheimers Dement, 17(3):327-406. https://doi.org/10.1002/alz.12328
World Health Organization. The top 10 causes of death. (accessed on 21 May 2021; https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death)
Almos, P. Z., Horváth, S., Czibula, A., Raskó, I., Sipos, B., Bihari, P., Béres, J., Juhász, A., Janka, Z., & Kálmán, J. (2008). H1 tau haplotype-related genomic variation at 17q21.3 as an Asian heritage of the European Gypsy population. Heredity (Edinb), 101(5), 416-419. https://doi.org/10.1038/hdy.2008.70
Alonso Adel, C., Mederlyova, A., Novak, M., Grundke-Iqbal, I., & Iqbal, K. (2004). Promotion of hyperphosphorylation by frontotemporal dementia tau mutations. J Biol Chem, 279(33), 34873-34881. https://doi.org/10.1074/jbc.M405131200
Alonso, M., Medina, J. H., & Pozzo-Miller, L. (2004). ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. Learn Mem, 11(2), 172-178. https://doi.org/10.1101/lm.67804
Andreadis, A., Broderick, J. A., & Kosik, K. S. (1995). Relative exon affinities and suboptimal splice site signals lead to non-equivalence of two cassette exons. Nucleic Acids Res, 23(17), 3585-3593. https://doi.org/10.1093/nar/23.17.3585
Andreadis, A., Brown, W. M., & Kosik, K. S. (1992). Structure and novel exons of the human tau gene. Biochemistry, 31(43), 10626-10633. https://doi.org/10.1021/bi00158a027
Arancibia, S., Silhol, M., Moulière, F., Meffre, J., Höllinger, I., Maurice, T., & Tapia-Arancibia, L. (2008). Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis, 31(3), 316-326. https://doi.org/10.1016/j.nbd.2008.05.012
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992). Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology, 42(3 Pt 1), 631-639. https://doi.org/10.1212/wnl.42.3.631
Augustinack, J. C., Schneider, A., Mandelkow, E. M., & Hyman, B. T. (2002). Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol, 103(1), 26-35. https://doi.org/10.1007/s004010100423
Bakoyiannis, I., Daskalopoulou, A., Pergialiotis, V., & Perrea, D. (2019). Phytochemicals and cognitive health: Are flavonoids doing the trick? Biomed Pharmacother, 109, 1488-1497. https://doi.org/10.1016/j.biopha.2018.10.086
Ballatore, C., Lee, V. M., & Trojanowski, J. Q. (2007). Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci, 8(9), 663-672. https://doi.org/10.1038/nrn2194
Barco, A., Pittenger, C., & Kandel, E. R. (2003). CREB, memory enhancement and the treatment of memory disorders: promises, pitfalls and prospects. Expert Opin Ther Targets, 7(1), 101-114. https://doi.org/10.1517/14728222.7.1.101
Barghorn, S., Zheng-Fischhöfer, Q., Ackmann, M., Biernat, J., von Bergen, M., Mandelkow, E. M., & Mandelkow, E. (2000). Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias. Biochemistry, 39(38), 11714-11721. https://doi.org/10.1021/bi000850r
Becker, R. E., & Giacobini, E. (1991). Cholinergic basis for Alzheimer therapy. Springer.
Bennett, D. A., Schneider, J. A., Wilson, R. S., Bienias, J. L., & Arnold, S. E. (2004). Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch Neurol, 61(3), 378-384. https://doi.org/10.1001/archneur.61.3.378
Berriman, J., Serpell, L. C., Oberg, K. A., Fink, A. L., Goedert, M., & Crowther, R. A. (2003). Tau filaments from human brain and from in vitro assembly of recombinant protein show cross-beta structure. Proc Natl Acad Sci U S A, 100(15), 9034-9038. https://doi.org/10.1073/pnas.1530287100
Bharani, K. L., Derex, R., Granholm, A. C., & Ledreux, A. (2017). A noradrenergic lesion aggravates the effects of systemic inflammation on the hippocampus of aged rats. PLoS One, 12(12), e0189821. https://doi.org/10.1371/journal.pone.0189821
Biancalana, M., & Koide, S. (2010). Molecular mechanism of Thioflavin-T binding to amyloid fibrils. Biochim Biophys Acta, 1804(7), 1405-1412. https://doi.org/10.1016/j.bbapap.2010.04.001
Biessels, G. J., Staekenborg, S., Brunner, E., Brayne, C., & Scheltens, P. (2006). Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol, 5(1), 64-74. https://doi.org/10.1016/s1474-4422(05)70284-2
Birks, J. (2006). Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev(1), Cd005593. https://doi.org/10.1002/14651858.Cd005593
Bobinski, M., de Leon, M. J., Tarnawski, M., Wegiel, J., Reisberg, B., Miller, D. C., & Wisniewski, H. M. (1998). Neuronal and volume loss in CA1 of the hippocampal formation uniquely predicts duration and severity of Alzheimer disease. Brain Res, 805(1-2), 267-269. https://doi.org/10.1016/s0006-8993(98)00759-8
Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H., & Nixon, R. A. (2008). Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. J Neurosci, 28(27), 6926-6937. https://doi.org/10.1523/jneurosci.0800-08.2008
Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., & Silva, A. J. (1994). Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell, 79(1), 59-68. https://doi.org/10.1016/0092-8674(94)90400-6
Braak, H., & Del Tredici, K. (2013). Amyloid-β may be released from non-junctional varicosities of axons generated from abnormal tau-containing brainstem nuclei in sporadic Alzheimer's disease: a hypothesis. Acta Neuropathol, 126(2), 303-306. https://doi.org/10.1007/s00401-013-1153-2
Braak, H., & Del Tredici, K. (2015). Neuroanatomy and pathology of sporadic Alzheimer's disease. Adv Anat Embryol Cell Biol, 215, 1-162. https://pubmed.ncbi.nlm.nih.gov/25920101/
Bramham, C. R., & Messaoudi, E. (2005). BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol, 76(2), 99-125. https://doi.org/10.1016/j.pneurobio.2005.06.003
Brunello, C. A., Merezhko, M., Uronen, R. L., & Huttunen, H. J. (2020). Mechanisms of secretion and spreading of pathological tau protein. Cell Mol Life Sci, 77(9), 1721-1744. https://doi.org/10.1007/s00018-019-03349-1
Buée, L., Bussière, T., Buée-Scherrer, V., Delacourte, A., & Hof, P. R. (2000). Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev, 33(1), 95-130. https://doi.org/10.1016/s0165-0173(00)00019-9
Calabrese, F., Guidotti, G., Racagni, G., & Riva, M. A. (2013). Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor. Neurobiol Aging, 34(12), 2768-2776. https://doi.org/10.1016/j.neurobiolaging.2013.06.014
Campioni, S., Mannini, B., Zampagni, M., Pensalfini, A., Parrini, C., Evangelisti, E., Relini, A., Stefani, M., Dobson, C. M., Cecchi, C., & Chiti, F. (2010). A causative link between the structure of aberrant protein oligomers and their toxicity. Nat Chem Biol, 6(2), 140-147. https://doi.org/10.1038/nchembio.283
Carlesimo, G. A., & Oscar-Berman, M. (1992). Memory deficits in Alzheimer's patients: a comprehensive review. Neuropsychol Rev, 3(2), 119-169. https://doi.org/10.1007/BF01108841
Carlyle, B. C., Nairn, A. C., Wang, M., Yang, Y., Jin, L. E., Simen, A. A., Ramos, B. P., Bordner, K. A., Craft, G. E., Davies, P., Pletikos, M., Šestan, N., Arnsten, A. F., & Paspalas, C. D. (2014). cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex. Proc Natl Acad Sci U S A, 111(13), 5036-5041. https://doi.org/10.1073/pnas.1322360111
Casey, D. A., Antimisiaris, D., & O'Brien, J. (2010). Drugs for Alzheimer's disease: are they effective? P t, 35(4), 208-211.
Chaudhary, A. R., Berger, F., Berger, C. L., & Hendricks, A. G. (2018). Tau directs intracellular trafficking by regulating the forces exerted by kinesin and dynein teams. Traffic, 19(2), 111-121. https://doi.org/10.1111/tra.12537
Chen, C., Wang, Z., Zhang, Z., Liu, X., Kang, S. S., Zhang, Y., & Ye, K. (2018). The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease. Proc Natl Acad Sci U S A, 115(3), 578-583. https://doi.org/10.1073/pnas.1718683115
Chen, J. J., Wang, T., An, C. D., Jiang, C. Y., Zhao, J., & Li, S. (2016). Brain-derived neurotrophic factor: a mediator of inflammation-associated neurogenesis in Alzheimer's disease. Rev Neurosci, 27(8), 793-811. https://doi.org/10.1515/revneuro-2016-0017
Chen, Y., Chen, Y., Liang, Y., Chen, H., Ji, X., & Huang, M. (2020). Berberine mitigates cognitive decline in an Alzheimer's disease mouse model by targeting both tau hyperphosphorylation and autophagic clearance. Biomed Pharmacother, 121, 109670. https://doi.org/10.1016/j.biopha.2019.109670
Cheng, C., & Liu, Z. G. (2019). Autophagy and the metabolism of misfolding protein. Adv Exp Med Biol, 1206, 375-420. https://doi.org/10.1007/978-981-15-0602-4_18
Chiu, Y. J., Hsieh, Y. H., Lin, T. H., Lee, G. C., Hsieh-Li, H. M., Sun, Y. C., Chen, C. M., Chang, K. H., & Lee-Chen, G. J. (2019). Novel compound VB-037 inhibits Aβ aggregation and promotes neurite outgrowth through enhancement of HSP27 and reduction of P38 and JNK-mediated inflammation in cell models for Alzheimer's disease. Neurochem Int, 125, 175-186. https://doi.org/ 10.1016/j.neuint.2019.01.021
Chong, F. P., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2018). Tau proteins and tauopathies in Alzheimer's disease. Cell Mol Neurobiol, 38(5), 965-980. https://doi.org/10.1007/s10571-017-0574-1
Chong, Y. H., Shin, Y. J., Lee, E. O., Kayed, R., Glabe, C. G., & Tenner, A. J. (2006). ERK1/2 activation mediates Abeta oligomer-induced neurotoxicity via caspase-3 activation and tau cleavage in rat organotypic hippocampal slice cultures. J Biol Chem, 281(29), 20315-20325. https://doi.org/10.1074/jbc.M601016200
Chung, S. H. (2009). Aberrant phosphorylation in the pathogenesis of Alzheimer's disease. BMB Rep, 42(8), 467-474. https://doi.org/10.5483/bmbrep.2009.42.8.467
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., Jucker, M., Goedert, M., & Tolnay, M. (2009). Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol, 11(7), 909-913. https://doi.org/10.1038/ncb1901
Clavaguera, F., Hench, J., Goedert, M., & Tolnay, M. (2015). Invited review: Prion-like transmission and spreading of tau pathology. Neuropathol Appl Neurobiol, 41(1), 47-58. https://doi.org/10.1111/nan.12197
Cronin-Golomb, A., Corkin, S., & Growdon, J. H. (1995). Visual dysfunction predicts cognitive deficits in Alzheimer's disease. Optom Vis Sci, 72(3), 168-176. https://doi.org/10.1097/00006324-199503000-00004
Crowther, R. A. (1991). Straight and paired helical filaments in Alzheimer disease have a common structural unit. Proc Natl Acad Sci U S A, 88(6), 2288-2292. https://doi.org/10.1073/pnas.88.6.2288
Cusack, C. L., Swahari, V., Hampton Henley, W., Michael Ramsey, J., & Deshmukh, M. (2013). Distinct pathways mediate axon degeneration during apoptosis and axon-specific pruning. Nat Commun, 4, 1876. https://doi.org/10.1038/ncomms2910
Davies, P., & Maloney, A. (1976). Selective loss of central cholinergic neurons in Alzheimer's disease. The Lancet, 308(8000), 1403. https://doi.org/10.1016/s0140-6736(76)91936-x
De-Paula, V. J., Schaeffer, E. L., Talib, L. L., Gattaz, W. F., & Forlenza, O. V. (2010). Inhibition of phospholipase A2 increases tau phosphorylation at Ser214 in embryonic rat hippocampal neurons. Prostaglandins Leukot Essent Fatty Acids, 82(1), 57-60. https://doi.org/10.1016/j.plefa.2009.07.006
Dickey, C. A., Kamal, A., Lundgren, K., Klosak, N., Bailey, R. M., Dunmore, J., Ash, P., Shoraka, S., Zlatkovic, J., Eckman, C. B., Patterson, C., Dickson, D. W., Nahman, N. S., Jr., Hutton, M., Burrows, F., & Petrucelli, L. (2007). The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest, 117(3), 648-658. https://doi.org/10.1172/jci29715
Dickson, D. W. (2004). Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect? J Clin Invest, 114(1), 23-27. https://doi.org/10.1172/jci22317
Drewes, G., Trinczek, B., Illenberger, S., Biernat, J., Schmitt-Ulms, G., Meyer, H. E., Mandelkow, E. M., & Mandelkow, E. (1995). Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262. J Biol Chem, 270(13), 7679-7688. https://doi.org/10.1074/jbc.270.13.7679
Driscoll, I., Davatzikos, C., An, Y., Wu, X., Shen, D., Kraut, M., & Resnick, S. M. (2009). Longitudinal pattern of regional brain volume change differentiates normal aging from MCI. Neurology, 72(22), 1906-1913. https://doi.org/10.1212/WNL.0b013e3181a82634
Duman, R. S. (2009). Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci, 11(3), 239-255. https://doi.org/10.31887/DCNS.2009.11.3/rsduman
Enz, A., Amstutz, R., Boddeke, H., Gmelin, G., & Malanowski, J. 1993. Brain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer’s disease. Prog Brain Res, 98, 431-438. https://doi.org/10.1016/s0079-6123(08)62429-2
Eschmann, N. A., Georgieva, E. R., Ganguly, P., Borbat, P. P., Rappaport, M. D., Akdogan, Y., Freed, J. H., Shea, J. E., & Han, S. (2017). Signature of an aggregation-prone conformation of tau. Sci Rep, 7, 44739. https://doi.org/10.1038/srep44739
Falcon, B., Cavallini, A., Angers, R., Glover, S., Murray, T. K., Barnham, L., Jackson, S., O'Neill, M. J., Isaacs, A. M., Hutton, M. L., Szekeres, P. G., Goedert, M., & Bose, S. (2015). Conformation determines the seeding potencies of native and recombinant Tau aggregates. J Biol Chem, 290(2), 1049-1065. https://doi.org/10.1074/jbc.M114.589309
Faraco, G., & Iadecola, C. (2013). Hypertension: a harbinger of stroke and dementia. Hypertension, 62(5), 810-817. https://doi.org/10.1161/hypertensionaha.113.01063
Fischer, D., Mukrasch, M. D., Biernat, J., Bibow, S., Blackledge, M., Griesinger, C., Mandelkow, E., & Zweckstetter, M. (2009). Conformational changes specific for pseudophosphorylation at serine 262 selectively impair binding of tau to microtubules. Biochemistry, 48(42), 10047-10055. https://doi.org/10.1021/bi901090m
Fitzpatrick, A. W. P., Falcon, B., He, S., Murzin, A. G., Murshudov, G., Garringer, H. J., Crowther, R. A., Ghetti, B., Goedert, M., & Scheres, S. H. W. (2017). Cryo-EM structures of tau filaments from Alzheimer's disease. Nature, 547(7662), 185-190. https://doi.org/10.1038/nature23002
Frausto, D. M., Forsyth, C. B., Keshavarzian, A., & Voigt, R. M. (2021). Dietary Regulation of Gut-Brain Axis in Alzheimer's Disease: Importance of Microbiota Metabolites. Front Neurosci, 15, 736814. https://doi.org/10.3389/fnins.2021.736814
Friedhoff, P., von Bergen, M., Mandelkow, E. M., Davies, P., & Mandelkow, E. (1998). A nucleated assembly mechanism of Alzheimer paired helical filaments. Proc Natl Acad Sci U S A, 95(26), 15712-15717. https://doi.org/10.1073/pnas.95.26.15712
Friedman, W. J. (2010). Proneurotrophins, seizures, and neuronal apoptosis. Neuroscientist, 16(3), 244-252. https://doi.org/10.1177/1073858409349903
Frost, B., Jacks, R. L., & Diamond, M. I. (2009). Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem, 284(19), 12845-12852. https://doi.org/10.1074/jbc.M808759200
Gamage, R., Wagnon, I., Rossetti, I., Childs, R., Niedermayer, G., Chesworth, R., & Gyengesi, E. (2020). Cholinergic modulation of glial function during aging and chronic neuroinflammation. Front Cell Neurosci, 14, 577912. https://doi.org/10.3389/fncel.2020.577912
Gandy, S., Simon, A. J., Steele, J. W., Lublin, A. L., Lah, J. J., Walker, L. C., Levey, A. I., Krafft, G. A., Levy, E., Checler, F., Glabe, C., Bilker, W. B., Abel, T., Schmeidler, J., & Ehrlich, M. E. (2010). Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid-beta oligomers. Ann Neurol, 68(2), 220-230. https://doi.org/10.1002/ana.22052
Gao, L., Tian, M., Zhao, H. Y., Xu, Q. Q., Huang, Y. M., Si, Q. C., Tian, Q., Wu, Q. M., Hu, X. M., Sun, L. B., McClintock, S. M., & Zeng, Y. (2016). TrkB activation by 7, 8-dihydroxyflavone increases synapse AMPA subunits and ameliorates spatial memory deficits in a mouse model of Alzheimer's disease. J Neurochem, 136(3), 620-636. https://doi.org/10.1111/jnc.13432
García-Ayllón, M. S., Small, D. H., Avila, J., & Sáez-Valero, J. (2011). Revisiting the role of acetylcholinesterase in Alzheimer's disease: Cross-talk with p-tau and β-amyloid. Front Mol Neurosci, 4, 22. https://doi.org/10.3389/fnmol.2011.00022
Gendron, T. F., & Petrucelli, L. (2009). The role of tau in neurodegeneration. Mol Neurodegener, 4(1), 1-19. https://doi.org/10.1186/1750-1326-4-13
Gerson, J. E., & Kayed, R. (2013). Formation and propagation of tau oligomeric seeds. Front Neurol, 4, 93. https://doi.org/10.3389/fneur.2013.00093
Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S. R., Jangamreddy, J. R., Mehrpour, M., Christoffersson, J., Chaabane, W., Moghadam, A. R., & Kashani, H. H. (2014). Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol, 112, 24-49. https://doi.org/10.1016/j.pneurobio.2013.10.004
Giacobini, E. (2002). Long-term stabilizing effect of cholinesterase inhibitors in the therapy of Alzheimer’disease. J Neural Transm Suppl(62), 181-187. https://doi.org/10.1007/978-3-7091-6139-5_17
Ginsberg, S. D., Alldred, M. J., Counts, S. E., Cataldo, A. M., Neve, R. L., Jiang, Y., Wuu, J., Chao, M. V., Mufson, E. J., Nixon, R. A., & Che, S. (2010). Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer's disease progression. Biol Psychiatry, 68(10), 885-893. https://doi.org/10.1016/j.biopsych.2010.05.030
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., & James, L. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349(6311), 704-706. https://doi.org/10.1038/349704a0
Goedert, M., Spillantini, M., Jakes, R., Rutherford, D., & Crowther, R. (1989). Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron, 3(4), 519-526. https://doi.org/10.1016/0896-6273(89)90210-9
Gong, C. X., Lidsky, T., Wegiel, J., Zuck, L., Grundke-Iqbal, I., & Iqbal, K. (2000). Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease. J Biol Chem, 275(8), 5535-5544. https://doi.org/10.1074/jbc.275.8.5535
Gong, C. X., Singh, T. J., Grundke-Iqbal, I., & Iqbal, K. (1993). Phosphoprotein phosphatase activities in Alzheimer disease brain. J Neurochem, 61(3), 921-927. https://doi.org/10.1111/j.1471-4159.1993.tb03603.x
Grober, E., Dickson, D., Sliwinski, M. J., Buschke, H., Katz, M., Crystal, H., & Lipton, R. B. (1999). Memory and mental status correlates of modified Braak staging. Neurobiol Aging, 20(6), 573-579. https://doi.org/10.1016/s0197-4580(99)00063-9
Guo, H., Albrecht, S., Bourdeau, M., Petzke, T., Bergeron, C., & LeBlanc, A. C. (2004). Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease. Am J Pathol, 165(2), 523-531. https://doi.org/10.1016/s0002-9440(10)63317-2
Guo, J. L., & Lee, V. M. (2013). Neurofibrillary tangle-like tau pathology induced by synthetic tau fibrils in primary neurons over-expressing mutant tau. FEBS Lett, 587(6), 717-723. https://doi.org/10.1016/j.febslet.2013.01.051
Guo, T., Noble, W., & Hanger, D. P. (2017). Roles of tau protein in health and disease. Acta Neuropathol, 133(5), 665-704. https://doi.org/10.1007/s00401-017-1707-9
Haase, C., Stieler, J. T., Arendt, T., & Holzer, M. (2004). Pseudophosphorylation of tau protein alters its ability for self-aggregation. J Neurochem, 88(6), 1509-1520. https://doi.org/10.1046/j.1471-4159.2003.02287.x
Hamsalakshmi, Alex, A. M., Arehally Marappa, M., Joghee, S., & Chidambaram, S. B. (2022). Therapeutic benefits of flavonoids against neuroinflammation: A systematic review. Inflammopharmacology, 30(1), 111-136. https://doi.org/10.1007/s10787-021-00895-8
Hamulakova, S., Janovec, L., Hrabinova, M., Spilovska, K., Korabecny, J., Kristian, P., Kuca, K., & Imrich, J. (2014). Synthesis and biological evaluation of novel tacrine derivatives and tacrine-coumarin hybrids as cholinesterase inhibitors. J Med Chem, 57(16), 7073-7084. https://doi.org/10.1021/jm5008648
Hanger, D. P., Anderton, B. H., & Noble, W. (2009). Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med, 15(3), 112-119. https://doi.org/10.1016/j.molmed.2009.01.003
Hanger, D. P., Byers, H. L., Wray, S., Leung, K. Y., Saxton, M. J., Seereeram, A., Reynolds, C. H., Ward, M. A., & Anderton, B. H. (2007). Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J Biol Chem, 282(32), 23645-23654. https://doi.org/10.1074/jbc.M703269200
Haniu, M., Talvenheimo, J., Le, J., Katta, V., Welcher, A., Rohde, M. F. (1995). Extracellular domain of neurotrophin receptor trkB: disulfide structure, N-glycosylation sites, and ligand binding. Arch Biochem Biophys, 322(1), 256-264. doi: 10.1006/abbi.1995.1460
Hartmann, A. M., Rujescu, D., Giannakouros, T., Nikolakaki, E., Goedert, M., Mandelkow, E. M., Gao, Q. S., Andreadis, A., & Stamm, S. (2001). Regulation of alternative splicing of human tau exon 10 by phosphorylation of splicing factors. Mol Cell Neurosci, 18(1), 80-90. https://doi.org/10.1006/mcne.2001.1000
Hernández, F., de Barreda, E. G., Fuster-Matanzo, A., Lucas, J. J., & Avila, J. (2010). GSK3: a possible link between beta amyloid peptide and tau protein. Exp Neurol, 223(2), 322-325. https://doi.org/10.1016/j.expneurol.2009.09.011
Hitchcock, S. A., & Pennington, L. D. (2006). Structure - brain exposure relationships. J Med Chem, 49(26), 7559-7583. https://doi.org/10.1021/jm060642i
Ho, V. M., Lee, J. A., & Martin, K. C. (2011). The cell biology of synaptic plasticity. Science, 334(6056), 623-628. https://doi.org/10.1126/science.1209236
Hock, C., Heese, K., Hulette, C., Rosenberg, C., & Otten, U. (2000). Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol, 57(6), 846-851. https://doi.org/10.1001/archneur.57.6.846
Hofer, M., Pagliusi, S. R., Hohn, A., Leibrock, J., & Barde, Y. A. (1990). Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J, 9(8), 2459-2464. https://pubmed.ncbi.nlm.nih.gov/2369898/
Hooper, C., Killick, R., & Lovestone, S. (2008). The GSK3 hypothesis of Alzheimer's disease. J Neurochem, 104(6), 1433-1439. https://doi.org/10.1111/j.1471-4159.2007.05194.x
Hooper, C., Meimaridou, E., Tavassoli, M., Melino, G., Lovestone, S., & Killick, R. (2007). p53 is upregulated in Alzheimer's disease and induces tau phosphorylation in HEK293a cells. Neurosci Lett, 418(1), 34-37. https://doi.org/10.1016/j.neulet.2007.03.026
Horch, H. W., & Katz, L. C. (2002). BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat Neurosci, 5(11), 1177-1184. https://doi.org/10.1038/nn927
Iqbal, K., Liu, F., & Gong, C. X. (2016). Tau and neurodegenerative disease: the story so far. Nat Rev Neurol, 12(1), 15-27. https://doi.org/10.1038/nrneurol.2015.225
Iwasaki, Y., Negishi, T., Inoue, M., Tashiro, T., Tabira, T., & Kimura, N. (2012). Sendai virus vector-mediated brain-derived neurotrophic factor expression ameliorates memory deficits and synaptic degeneration in a transgenic mouse model of Alzheimer's disease. J Neurosci Res, 90(5), 981-989. https://doi.org/10.1002/jnr.22830
Jameel, E., Umar, T., Kumar, J., & Hoda, N. (2016). Coumarin: A privileged scaffold for the design and development of antineurodegenerative agents. Chem Biol Drug Des, 87(1), 21-38. https://doi.org/10.1111/cbdd.12629
Jang, S. W., Liu, X., Yepes, M., Shepherd, K. R., Miller, G. W., Liu, Y., Wilson, W. D., Xiao, G., Blanchi, B., Sun, Y. E., & Ye, K. (2010). A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci U S A, 107(6), 2687-2692. https://doi.org/10.1073/pnas.0913572107
Jiao, S. S., Shen, L. L., Zhu, C., Bu, X. L., Liu, Y. H., Liu, C. H., Yao, X. Q., Zhang, L. L., Zhou, H. D., Walker, D. G., Tan, J., Götz, J., Zhou, X. F., & Wang, Y. J. (2016). Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease. Transl Psychiatry, 6(10), e907. https://doi.org/10.1038/tp.2016.186
Johannessen, M., & Moens, U. (2007). Multisite phosphorylation of the cAMP response element-binding protein (CREB) by a diversity of protein kinases. Front Biosci, 12, 1814-1832. https://doi.org/10.2741/2190
Johnson, G. V., & Jenkins, S. M. (1999). Tau protein in normal and Alzheimer’s disease brain. J Alzheimers Dis(4-5), 307-328. https://doi.org/10.3233/jad-1999-14-511
Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., Hoyte, K., Gustafson, A., Liu, Y., Lu, Y., Bhangale, T., Graham, R. R., Huttenlocher, J., Bjornsdottir, G., Andreassen, O. A., . . . Stefansson, K. (2012). A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature, 488(7409), 96-99. https://doi.org/10.1038/nature11283
Kaduszkiewicz, H., Zimmermann, T., Beck-Bornholdt, H. P., & van den Bussche, H. (2005). Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. Bmj, 331(7512), 321-327. https://doi.org/10.1136/bmj.331.7512.321
Kaldun, J. C., & Sprecher, S. G. (2019). Initiated by CREB: Resolving gene regulatory programs in learning and memory: Switch in cofactors and transcription regulators between memory consolidation and maintenance network. Bioessays, 41(8), e1900045. https://doi.org/10.1002/bies.201900045
Kamiloglu, S., Sari, G., Ozdal, T., & Capanoglu, E. (2020). Guidelines for cell viability assays. Food Frontiers, 1(3), 332-349. https://onlinelibrary.wiley.com/doi/full/10.1002/fft2.44
Kandel, E. R. (2012). The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain, 5, 14. https://doi.org/10.1186/1756-6606-5-14
Kaplan, D. R., & Miller, F. D. (2000). Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol, 10(3), 381-391. https://doi.org/10.1016/s0959-4388(00)00092-1
Katoh-Semba, R., Asano, T., Ueda, H., Morishita, R., Takeuchi, I. K., Inaguma, Y., & Kato, K. (2002). Riluzole enhances expression of brain-derived neurotrophic factor with consequent proliferation of granule precursor cells in the rat hippocampus. FASEB J, 16(10), 1328-1330. https://doi.org/10.1096/fj.02-0143fje
Kaushal, V., Dye, R., Pakavathkumar, P., Foveau, B., Flores, J., Hyman, B., Ghetti, B., Koller, B. H., & LeBlanc, A. C. (2015). Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ, 22(10), 1676-1686. https://doi.org/10.1038/cdd.2015.16
Kayed, R., & Lasagna-Reeves, C. A. (2013). Molecular mechanisms of amyloid oligomers toxicity. J Alzheimers Dis, 33 Suppl 1, S67-78. https://doi.org/10.3233/jad-2012-129001
Kfoury, N., Holmes, B. B., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2012). Trans-cellular propagation of Tau aggregation by fibrillar species. J Biol Chem, 287(23), 19440-19451. https://doi.org/10.1074/jbc.M112.346072
Kida, S., & Serita, T. (2014). Functional roles of CREB as a positive regulator in the formation and enhancement of memory. Brain Res Bull, 105, 17-24. https://doi.org/10.1016/j.brainresbull.2014.04.011
Kidd, M. (1963). Paired helical filaments in electron microscopy of Alzheimer's disease. Nature, 197, 192-193. https://doi.org/10.1038/197192b0
Kim, D., Lim, S., Haque, M. M., Ryoo, N., Hong, H. S., Rhim, H., Lee, D. E., Chang, Y. T., Lee, J. S., Cheong, E., Kim, D. J., & Kim, Y. K. (2015). Identification of disulfide cross-linked tau dimer responsible for tau propagation. Sci Rep, 5, 15231. https://doi.org/10.1038/srep15231
Kumar, S., & Pandey, A. K. (2013). Chemistry and biological activities of flavonoids: an overview. Sci. World J, 2013, 162750. https://doi.org/10.1155/2013/162750
Kurbatskaya, K., Phillips, E. C., Croft, C. L., Dentoni, G., Hughes, M. M., Wade, M. A., Al-Sarraj, S., Troakes, C., O'Neill, M. J., Perez-Nievas, B. G., Hanger, D. P., & Noble, W. (2016). Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer's disease brain. Acta Neuropathol Commun, 4, 34. https://doi.org/10.1186/s40478-016-0299-2
La Joie, R., Ayakta, N., Seeley, W. W., Borys, E., Boxer, A. L., DeCarli, C., Doré, V., Grinberg, L. T., Huang, E., Hwang, J. H., Ikonomovic, M. D., Jack, C., Jr., Jagust, W. J., Jin, L. W., Klunk, W. E., Kofler, J., Lesman-Segev, O. H., Lockhart, S. N., Lowe, V. J., . . . Rabinovici, G. D. (2019). Multisite study of the relationships between antemortem [(11)C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. Alzheimers Dement, 15(2), 205-216. https://doi.org/10.1016/j.jalz.2018.09.001
LaPointe, N. E., Morfini, G., Pigino, G., Gaisina, I. N., Kozikowski, A. P., Binder, L. I., & Brady, S. T. (2009). The amino terminus of tau inhibits kinesin‐dependent axonal transport: implications for filament toxicity. J Neurosci Res, 87(2), 440-451. https://doi.org/10.1002/jnr.21850
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., & Kayed, R. (2012). Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau. Sci Rep, 2, 700. https://doi.org/10.1038/srep00700
LeBlanc, A. C., Ramcharitar, J., Afonso, V., Hamel, E., Bennett, D. A., Pakavathkumar, P., & Albrecht, S. (2014). Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment. Cell Death Differ, 21(5), 696-706. https://doi.org/10.1038/cdd.2013.194
Lee, G., Neve, R. L., & Kosik, K. S. (1989). The microtubule binding domain of tau protein. Neuron, 2(6), 1615-1624. https://doi.org/10.1016/0896-6273(89)90050-0
Lee, G., & Leugers, C. J. (2012). Tau and tauopathies. Prog Mol Biol Transl Sci, 107, 263-293. https://doi.org/10.1016/b978-0-12-385883-2.00004-7
Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C. E., Jondro, P. D., Schmidt, S. D., & Wang, K. (1995). Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science, 269(5226), 973-977. https://doi.org/10.1126/science.7638622
Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Paul Murphy, M., Baker, M., Yu, X., Duff, K., Hardy, J., Corral, A., Lin, W. L., Yen, S. H., Dickson, D. W., Davies, P., & Hutton, M. (2000). Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet, 25(4), 402-405. https://doi.org/10.1038/78078
Li, C., & Götz, J. (2017). Tau-based therapies in neurodegeneration: opportunities and challenges. Nat Rev Drug Discov, 16(12), 863-883. https://doi.org/10.1038/nrd.2017.155
Li, H., Yao, Y., & Li, L. (2017). Coumarins as potential antidiabetic agents. J Pharm Pharmacol, 69(10), 1253-1264. https://doi.org/10.1111/jphp.12774
Li, N., & Liu, G. T. (2010). The novel squamosamide derivative FLZ enhances BDNF/TrkB/CREB signaling and inhibits neuronal apoptosis in APP/PS1 mice. Acta Pharmacol Sin, 31(3), 265-272. https://doi.org/10.1038/aps.2010.3
Liang, Y., Ye, C., Chen, Y., Chen, Y., Diao, S., & Huang, M. (2021). Berberine improves behavioral and cognitive deficits in a mouse model of Alzheimer's disease via regulation of β-amyloid production and endoplasmic reticulum stress. ACS Chem Neurosci, 12(11), 1894-1904. https://doi.org/10.1021/acschemneuro.0c00808
Lin, T. H., Chiu, Y. J., Lin, C. H., Lin, C. Y., Chao, C. Y., Chen, Y. C., Yang, S. M., Lin, W., Mei Hsieh-Li, H., Wu, Y. R., Chang, K. H., Lee-Chen, G. J., & Chen, C. M. (2020). Exploration of multi-target effects of 3-benzoyl-5-hydroxychromen-2-one in Alzheimer's disease cell and mouse models. Aging Cell, 19(7), e13169. https://doi.org/10.1111/acel.13169
Liu, C. C., Liu, C. C., Kanekiyo, T., Xu, H., & Bu, G. (2013). Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol, 9(2), 106-118. https://doi.org/10.1038/nrneurol.2012.263
Liu, F., Grundke-Iqbal, I., Iqbal, K., & Gong, C. X. (2005). Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur J Neurosci, 22(8), 1942-1950. https://doi.org/10.1111/j.1460-9568.2005.04391.x
Liu, F., & Gong, C. X. (2008). Tau exon 10 alternative splicing and tauopathies. Mol Neurodegener, 3, 8. https://doi.org/10.1186/1750-1326-3-8
Liu, H., Wang, L., Lv, M., Pei, R., Li, P., Pei, Z., Wang, Y., Su, W., & Xie, X. Q. (2014). AlzPlatform: an Alzheimer's disease domain-specific chemogenomics knowledgebase for polypharmacology and target identification research. J Chem Inf Model, 54(4), 1050-1060. https://doi.org/10.1021/ci500004h
Liu, X., Obianyo, O., Chan, C.B., Huang, J., Xue, S., Yang, J.J., Zeng, F., Goodman, M., & Ye, K. (2014). Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the TrkB receptor. J Biol Chem, 289(40), 27571-27584. https://doi.org/10.1074/jbc.M114.562561
Lonze, B. E., & Ginty, D. D. (2002). Function and regulation of CREB family transcription factors in the nervous system. Neuron, 35(4), 605-623. https://doi.org/10.1016/s0896-6273(02)00828-0
Lucas, J. J., Hernández, F., Gómez-Ramos, P., Morán, M. A., Hen, R., & Avila, J. (2001). Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J, 20(1-2), 27-39. https://doi.org/10.1093/emboj/20.1.27
Mandelkow, E. M., Biernat, J., Drewes, G., Gustke, N., Trinczek, B., & Mandelkow, E. (1995). Tau domains, phosphorylation, and interactions with microtubules. Neurobiol Aging, 16(3), 355-362; discussion 362-353. https://doi.org/10.1016/0197-4580(95)00025-a
Margittai, M., & Langen, R. (2006). Side chain-dependent stacking modulates tau filament structure. J Biol Chem, 281(49), 37820-37827. https://doi.org/10.1074/jbc.M605336200
Martin, L., Latypova, X., & Terro, F. (2011). Post-translational modifications of tau protein: implications for Alzheimer's disease. Neurochem Int, 58(4), 458-471. https://doi.org/10.1016/j.neuint.2010.12.023
Massa, S. M., Yang, T., Xie, Y., Shi, J., Bilgen, M., Joyce, J. N., Nehama, D., Rajadas, J., & Longo, F. M. (2010). Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J Clin Invest, 120(5), 1774-1785. https://doi.org/10.1172/jci41356
Matos, M. J., Vilar, S., Gonzalez-Franco, R. M., Uriarte, E., Santana, L., Friedman, C., Tatonetti, N. P., Viña, D., & Fontenla, J. A. (2013). Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study. Eur J Med Chem, 63, 151-161. https://doi.org/10.1016/j.ejmech.2013.02.009
Mattson, M. P., Maudsley, S., & Martin, B. (2004). BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci, 27(10), 589-594. https://doi.org/10.1016/j.tins.2004.08.001
McAllister, A. K. (2002). Spatially restricted actions of BDNF. Neuron, 36(4), 549-550. https://doi.org/10.1016/s0896-6273(02)01063-2
McAllister, A. K., Katz, L. C., & Lo, D. C. (1999). Neurotrophins and synaptic plasticity. Annu Rev Neurosci, 22, 295-318. https://doi.org/10.1146/annurev.neuro.22.1.295
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology, 34(7), 939-944. https://doi.org/10.1212/wnl.34.7.939
Meraz-Ríos, M. A., Lira-De León, K. I., Campos-Peña, V., De Anda-Hernández, M. A., & Mena-López, R. (2010). Tau oligomers and aggregation in Alzheimer's disease. J Neurochem, 112(6), 1353-1367. https://doi.org/10.1111/j.1471-4159.2009.06511.x
Mesulam, M. M., & Geula, C. (1990). Shifting patterns of cortical cholinesterases in Alzheimer's disease: implications for treatment, diagnosis, and pathogenesis. Adv Neurol, 51, 235-240. https://pubmed.ncbi.nlm.nih.gov/2403715/
Meyer, V., Dinkel, P. D., Luo, Y., Yu, X., Wei, G., Zheng, J., Eaton, G. R., Ma, B., Nussinov, R., Eaton, S. S., & Margittai, M. (2014). Single mutations in tau modulate the populations of fibril conformers through seed selection. Angew Chem Int Ed Engl, 53(6), 1590-1593. https://doi.org/10.1002/anie.201308473
Miranda, M., Morici, J. F., Zanoni, M. B., & Bekinschtein, P. (2019). Brain-derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci, 13, 363. https://doi.org/10.3389/fncel.2019.00363
Moor, L. F. E., Vasconcelos, T. R. A., da, R. R. R., Pinto, L. S. S., & da Costa, T. M. (2021). Quinoline: An Attractive Scaffold in Drug Design. Mini Rev Med Chem, 21(16), 2209-2226. https://doi.org/10.2174/1389557521666210210155908
Morrison, R. S., Kinoshita, Y., Johnson, M. D., Guo, W., & Garden, G. A. (2003). p53-dependent cell death signaling in neurons. Neurochem Res, 28(1), 15-27. https://doi.org/10.1023/a:1021687810103
Nagahara, A. H., Merrill, D. A., Coppola, G., Tsukada, S., Schroeder, B. E., Shaked, G. M., Wang, L., Blesch, A., Kim, A., Conner, J. M., Rockenstein, E., Chao, M. V., Koo, E. H., Geschwind, D., Masliah, E., Chiba, A. A., & Tuszynski, M. H. (2009). Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med, 15(3), 331-337. https://doi.org/10.1038/nm.1912
Nagappan, G., & Lu, B. (2005). Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications. Trends Neurosci, 28(9), 464-471. https://doi.org/10.1016/j.tins.2005.07.003
Neve, R. L., Harris, P., Kosik, K. S., Kurnit, D. M., & Donlon, T. A. (1986). Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. Brain Res, 387(3), 271-280. https://doi.org/10.1016/0169-328x(86)90033-1
Nikolaev, A., McLaughlin, T., O'Leary, D. D., & Tessier-Lavigne, M. (2009). APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature, 457(7232), 981-989. https://doi.org/10.1038/nature07767
Novak, M., Kabat, J., & Wischik, C. M. (1993). Molecular characterization of the minimal protease resistant tau unit of the Alzheimer's disease paired helical filament. EMBO J, 12(1), 365-370.
Obi, K., Akiyama, H., Kondo, H., Shimomura, Y., Hasegawa, M., Iwatsubo, T., Mizuno, Y., & Mochizuki, H. (2008). Relationship of phosphorylated α-synuclein and tau accumulation to Aβ deposition in the cerebral cortex of dementia with Lewy bodies. Exp Neurol, 210(2), 409-420. https://doi.org/10.1016/j.expneurol.2007.11.019
Ochs, G., Penn, R. D., York, M., Giess, R., Beck, M., Tonn, J., Haigh, J., Malta, E., Traub, M., Sendtner, M., & Toyka, K. V. (2000). A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord, 1(3), 201-206. https://doi.org/10.1080/14660820050515197
Ozer, R. S., & Halpain, S. (2000). Phosphorylation-dependent localization of microtubule-associated protein MAP2c to the actin cytoskeleton. Mol Biol Cell, 11(10), 3573-3587. https://doi.org/10.1091/mbc.11.10.3573
Panda, D., Samuel, J. C., Massie, M., Feinstein, S. C., & Wilson, L. (2003). Differential regulation of microtubule dynamics by three- and four-repeat tau: implications for the onset of neurodegenerative disease. Proc Natl Acad Sci U S A, 100(16), 9548-9553. https://doi.org/10.1073/pnas.1633508100
Paranjape, G. S., Gouwens, L. K., Osborn, D. C., & Nichols, M. R. (2012). Isolated amyloid-β(1-42) protofibrils, but not isolated fibrils, are robust stimulators of microglia. ACS Chem Neurosci, 3(4), 302-311. https://doi.org/10.1021/cn2001238
Park, S. A., Ahn, S. I., & Gallo, J. M. (2016). Tau mis-splicing in the pathogenesis of neurodegenerative disorders. BMB Rep, 49(8), 405-413. https://doi.org/10.5483/bmbrep.2016.49.8.084
Paspalas, C. D., Carlyle, B. C., Leslie, S., Preuss, T. M., Crimins, J. L., Huttner, A. J., van Dyck, C. H., Rosene, D. L., Nairn, A. C., & Arnsten, A. F. T. (2018). The aged rhesus macaque manifests Braak stage III/IV Alzheimer's-like pathology. Alzheimers Dement, 14(5), 680-691. https://doi.org/10.1016/j.jalz.2017.11.005
Peng, S., Wuu, J., Mufson, E. J., & Fahnestock, M. (2005). Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. J Neurochem, 93(6), 1412-1421. https://doi.org/10.1111/j.1471-4159.2005.03135.x
Perry, E., Perry, R., Blessed, G., & Tomlinson, B. (1977). Necropsy evidence of central cholinergic deficits in senile dementia. Lancet, 309(8004), 189. https://doi.org/10.1016/s0140-6736(77)91780-9
Phillips, H. S., Hains, J. M., Armanini, M., Laramee, G. R., Johnson, S. A., & Winslow, J. W. (1991). BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease. Neuron, 7(5), 695-702. https://doi.org/10.1016/0896-6273(91)90273-3
Poduslo, J. F., & Curran, G. L. (1996). Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res Mol Brain Res, 36(2), 280-286. https://doi.org/10.1016/0169-328x(95)00250-v
Pradhan, J., Noakes, P. G., & Bellingham, M. C. (2019). The Role of Altered BDNF/TrkB Signaling in Amyotrophic Lateral Sclerosis. Front Cell Neurosci, 13, 368. https://doi.org/10.3389/fncel.2019.00368
Price, J. L., Ko, A. I., Wade, M. J., Tsou, S. K., McKeel, D. W., & Morris, J. C. (2001). Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol, 58(9), 1395-1402. https://doi.org/10.1001/archneur.58.9.1395
Prince, M., Albanese, E., Guerchet, M., & Prina, M. (2014). World Alzheimer Report 2014. Dementia and risk reduction. Alzheimers Disease International, London.
Präbst, K., Engelhardt, H., Ringgeler, S., & Hübner, H. (2017). Cell Viability Assays. Methods in Molecular Biology.
Qian, W., Shi, J., Yin, X., Iqbal, K., Grundke-Iqbal, I., Gong, C.-X., & Liu, F. (2010). PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3β. J Alzheimer Dis, 19(4), 1221-1229. https://doi.org/10.3233/JAD-2010-1317
Qin, Q., Teng, Z., Liu, C., Li, Q., Yin, Y., & Tang, Y. (2021). TREM2, microglia, and Alzheimer's disease. Mech Ageing Dev, 195, 111438. https://doi.org/10.1016/j.mad.2021.111438
Qizilbash, N., Whitehead, A., Higgins, J., Wilcock, G., Schneider, L., & Farlow, M. (1998). Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration. Jama, 280(20), 1777-1782. https://doi.org/10.1001/jama.280.20.1777
Radecki, D. T., Brown, L. M., Martinez, J., & Teyler, T. J. (2005). BDNF protects against stress-induced impairments in spatial learning and memory and LTP. Hippocampus, 15(2), 246-253. https://doi.org/10.1002/hipo.20048
Raff, M. C., Whitmore, A. V., & Finn, J. T. (2002). Axonal self-destruction and neurodegeneration. Science, 296(5569), 868-871. https://doi.org/10.1126/science.1068613
Ramalho, R. M., Ribeiro, P. S., Solá, S., Castro, R. E., Steer, C. J., & Rodrigues, C. M. (2004). Inhibition of the E2F-1/p53/Bax pathway by tauroursodeoxycholic acid in amyloid beta-peptide-induced apoptosis of PC12 cells. J Neurochem, 90(3), 567-575. https://doi.org/10.1111/j.1471-4159.2004.02517.x
Rankin, C. A., Sun, Q., & Gamblin, T. C. (2008). Pre-assembled tau filaments phosphorylated by GSK-3β form large tangle-like structures. Neurobiol Dis, 31(3), 368-377. https://doi.org/10.1016/j.nbd.2008.05.011
Rapoport, M., Dawson, H. N., Binder, L. I., Vitek, M. P., & Ferreira, A. (2002). Tau is essential to β-amyloid-induced neurotoxicity. Proc Natl Acad Sci U S A, 99(9), 6364-6369. https://doi.org/10.1073/pnas.092136199
Rastogi, R., Jiang, Z., Ahmad, N., Rosati, R., Liu, Y., Beuret, L., Monks, R., Charron, J., Birnbaum, M. J., & Samavati, L. (2013). Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways. J Biol Chem, 288(47), 33966-33977. https://doi.org/10.1074/jbc.M113.492702
Rees, T. M., & Brimijoin, S. (2003). The role of acetylcholinesterase in the pathogenesis of Alzheimer's disease. Drugs Today (Barc), 39(1), 75-83. https://doi.org/10.1358/dot.2003.39.1.740206
Ricci, J. E., Gottlieb, R. A., & Green, D. R. (2003). Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis. J Cell Biol, 160(1), 65-75. https://doi.org/10.1083/jcb.200208089
Rosa, E., & Fahnestock, M. (2015). CREB expression mediates amyloid β-induced basal BDNF downregulation. Neurobiol Aging, 36(8), 2406-2413. https://doi.org/10.1016/j.neurobiolaging.2015.04.014
Sadleir, K. R., Kandalepas, P. C., Buggia-Prévot, V., Nicholson, D. A., Thinakaran, G., & Vassar, R. (2016). Presynaptic dystrophic neurites surrounding amyloid plaques are sites of microtubule disruption, BACE1 elevation, and increased Aβ generation in Alzheimer's disease. Acta Neuropathol, 132(2), 235-256. https://doi.org/10.1007/s00401-016-1558-9
Sahara, N., Maeda, S., Murayama, M., Suzuki, T., Dohmae, N., Yen, S. H., & Takashima, A. (2007). Assembly of two distinct dimers and higher-order oligomers from full-length tau. Eur J Neurosci, 25(10), 3020-3029. https://doi.org/10.1111/j.1460-9568.2007.05555.x
Sarkar, S. (2013). Regulation of autophagy by mTOR-dependent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers. Biochemical Society Transactions, 41(5), 1103-1130. https://doi.org/10.1042/BST20130134
Schleich, K., & Lavrik, I. N. (2013). Mathematical modeling of apoptosis. Cell Commun Signal, 11(1), 44. https://doi.org/10.1186/1478-811x-11-44
Schoenmann, Z., Assa-Kunik, E., Tiomny, S., Minis, A., Haklai-Topper, L., Arama, E., & Yaron, A. (2010). Axonal degeneration is regulated by the apoptotic machinery or a NAD+-sensitive pathway in insects and mammals. J Neurosci, 30(18), 6375-6386. https://doi.org/10.1523/jneurosci.0922-10.2010
Sengupta, A., Kabat, J., Novak, M., Wu, Q., Grundke-Iqbal, I., & Iqbal, K. (1998). Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules. Arch Biochem Biophys, 357(2), 299-309. https://doi.org/10.1006/abbi.1998.0813
Sengupta, U., Nilson, A. N., & Kayed, R. (2016). The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine, 6, 42-49. https://doi.org/10.1016/j.ebiom.2016.03.035
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med, 1(1), a006189. https://doi.org/10.1101/cshperspect.a006189
Shaaban, S. (2010). Synthesis and biological activity of multifunctional sensor/effector catalysts.
Shimabukuro, J., Awata, S., & Matsuoka, H. (2005). Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients. Psychiatry Clin Neurosci, 59(3), 274-279. https://doi.org/10.1111/j.1440-1819.2005.01371.x
Simon, D. J., Weimer, R. M., McLaughlin, T., Kallop, D., Stanger, K., Yang, J., O'Leary, D. D., Hannoush, R. N., & Tessier-Lavigne, M. (2012). A caspase cascade regulating developmental axon degeneration. J Neurosci, 32(49), 17540-17553. https://doi.org/10.1523/jneurosci.3012-12.2012
Singh, K. K., Park, K. J., Hong, E. J., Kramer, B. M., Greenberg, M. E., Kaplan, D. R., & Miller, F. D. (2008). Developmental axon pruning mediated by BDNF-p75NTR-dependent axon degeneration. Nat Neurosci, 11(6), 649-658. https://doi.org/10.1038/nn.2114
Singh, P., Singh, D., & Goel, R. K. (2014). Phytoflavonoids: antiepileptics for the future. channels (retigabine), 3, 5.
Sloane, J. A., Pietropaolo, M. F., Rosene, D. L., Moss, M. B., Peters, A., Kemper, T., & Abraham, C. R. (1997). Lack of correlation between plaque burden and cognition in the aged monkey. Acta Neuropathol, 94(5), 471-478. https://doi.org/10.1007/s004010050735
Small, S. A., Simoes-Spassov, S., Mayeux, R., & Petsko, G. A. (2017). Endosomal traffic jams represent a pathogenic hub and therapeutic target in Alzheimer's disease. Trends Neurosci, 40(10), 592-602. https://doi.org/10.1016/j.tins.2017.08.003
Sotiropoulos, I., Galas, M. C., Silva, J. M., Skoulakis, E., Wegmann, S., Maina, M. B., Blum, D., Sayas, C. L., Mandelkow, E. M., Mandelkow, E., Spillantini, M. G., Sousa, N., Avila, J., Medina, M., Mudher, A., & Buee, L. (2017). Atypical, non-standard functions of the microtubule associated Tau protein. Acta Neuropathol Commun, 5(1), 91. https://doi.org/10.1186/s40478-017-0489-6
Srikrishna, D., Godugu, C., & Dubey, P. K. (2018). A Review on Pharmacological Properties of Coumarins. Mini Rev Med Chem, 18(2), 113-141. https://doi.org/10.2174/1389557516666160801094919
Stagni, F., Giacomini, A., Guidi, S., Emili, M., Uguagliati, B., Salvalai, M. E., Bortolotto, V., Grilli, M., Rimondini, R., & Bartesaghi, R. (2017). A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS. Exp Neurol, 298(Pt A), 79-96. https://doi.org/10.1016/j.expneurol.2017.08.018
Stefanatos, R., & Sanz, A. (2018). The role of mitochondrial ROS in the aging brain. FEBS Lett, 592(5), 743-758. https://doi.org/10.1002/1873-3468.12902
Su, J. H., Deng, G., & Cotman, C. W. (1997). Bax protein expression is increased in Alzheimer's brain: correlations with DNA damage, Bcl-2 expression, and brain pathology. J Neuropathol Exp Neurol, 56(1), 86-93. https://doi.org/10.1097/00005072-199701000-00009
Suvà, D., Favre, I., Kraftsik, R., Esteban, M., Lobrinus, A., & Miklossy, J. (1999). Primary motor cortex involvement in Alzheimer disease. J Neuropathol Exp Neurol, 58(11), 1125-1134. https://doi.org/10.1097/00005072-199911000-00002
Tao, X., Finkbeiner, S., Arnold, D. B., Shaywitz, A. J., & Greenberg, M. E. (1998). Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron, 20(4), 709-726. https://doi.org/10.1016/s0896-6273(00)81010-7
Tapia-Arancibia, L., Aliaga, E., Silhol, M., & Arancibia, S. (2008). New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Res Rev, 59(1), 201-220. https://doi.org/10.1016/j.brainresrev.2008.07.007
Teri, L., McCurry, S. M., & Logsdon, R. G. (1997). Memory, thinking, and aging. What we know about what we know. West J Med, 167(4), 269-275. https://pubmed.ncbi.nlm.nih.gov/9348759/
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991). Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol, 30(4), 572-580. https://doi.org/10.1002/ana.410300410
Terwel, D., Lasrado, R., Snauwaert, J., Vandeweert, E., Van Haesendonck, C., Borghgraef, P., & Van Leuven, F. (2005). Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of Tau-4R/2N transgenic mice. J Biol Chem, 280(5), 3963-3973. https://doi.org/10.1074/jbc.M409876200
Timmusk, T., Palm, K., Metsis, M., Reintam, T., Paalme, V., Saarma, M., & Persson, H. (1993). Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron, 10(3), 475-489. https://doi.org/10.1016/0896-6273(93)90335-o
Torres, A. K., Rivera, B. I., Polanco, C. M., Jara, C., & Tapia-Rojas, C. (2022). Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer's disease. Neural Regen Res, 17(8), 1645-1651. https://doi.org/10.4103/1673-5374.332125
Tseng, B. P., Green, K. N., Chan, J. L., Blurton-Jones, M., & LaFerla, F. M. (2008). Aβ inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol Aging, 29(11), 1607-1618. https://doi.org/10.1016/j.neurobiolaging.2007.04.014
Ulrich, J., Meier-Ruge, W., Probst, A., Meier, E., & Ipsen, S. (1990). Senile plaques: staining for acetylcholinesterase and A4 protein: a comparative study in the hippocampus and entorhinal cortex. Acta Neuropathol, 80(6), 624-628. https://doi.org/10.1007/bf00307630
Uribe, V., Wong, B. K., Graham, R. K., Cusack, C. L., Skotte, N. H., Pouladi, M. A., Xie, Y., Feinberg, K., Ou, Y., Ouyang, Y., Deng, Y., Franciosi, S., Bissada, N., Spreeuw, A., Zhang, W., Ehrnhoefer, D. E., Vaid, K., Miller, F. D., Deshmukh, M., . . . Hayden, M. R. (2012). Rescue from excitotoxicity and axonal degeneration accompanied by age-dependent behavioral and neuroanatomical alterations in caspase-6-deficient mice. Hum Mol Genet, 21(9), 1954-1967. https://doi.org/10.1093/hmg/dds005
Varani, L., Hasegawa, M., Spillantini, M. G., Smith, M. J., Murrell, J. R., Ghetti, B., Klug, A., Goedert, M., & Varani, G. (1999). Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17. Proc Natl Acad Sci U S A, 96(14), 8229-8234. https://doi.org/10.1073/pnas.96.14.8229
Vauzour, D., Vafeiadou, K., Rodriguez-Mateos, A., Rendeiro, C., & Spencer, J. P. (2008). The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr, 3(3-4), 115-126. https://doi.org/10.1007/s12263-008-0091-4
Vohra, B. P., Sasaki, Y., Miller, B. R., Chang, J., DiAntonio, A., & Milbrandt, J. (2010). Amyloid precursor protein cleavage-dependent and -independent axonal degeneration programs share a common nicotinamide mononucleotide adenylyltransferase 1-sensitive pathway. J Neurosci, 30(41), 13729-13738. https://doi.org/10.1523/jneurosci.2939-10.2010
Volosin, M., Song, W., Almeida, R. D., Kaplan, D. R., Hempstead, B. L., & Friedman, W. J. (2006). Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J Neurosci, 26(29), 7756-7766. https://doi.org/10.1523/jneurosci.1560-06.2006
von Bergen, M., Barghorn, S., Li, L., Marx, A., Biernat, J., Mandelkow, E. M., & Mandelkow, E. (2001). Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. J Biol Chem, 276(51), 48165-48174. https://doi.org/10.1074/jbc.M105196200
von Bergen, M., Barghorn, S., Müller, S. A., Pickhardt, M., Biernat, J., Mandelkow, E. M., Davies, P., Aebi, U., & Mandelkow, E. (2006). The core of tau-paired helical filaments studied by scanning transmission electron microscopy and limited proteolysis. Biochemistry, 45(20), 6446-6457. https://doi.org/10.1021/bi052530j
von Bergen, M., Friedhoff, P., Biernat, J., Heberle, J., Mandelkow, E. M., & Mandelkow, E. (2000). Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming beta structure. Proc Natl Acad Sci U S A, 97(10), 5129-5134. https://doi.org/10.1073/pnas.97.10.5129
Walker, D., Lue, L. F., Paul, G., Patel, A., & Sabbagh, M. N. (2015). Receptor for advanced glycation endproduct modulators: a new therapeutic target in Alzheimer's disease. Expert Opin Investig Drugs, 24(3), 393-399. https://doi.org/10.1517/13543784.2015.1001490
Wang, J. Z., Grundke-Iqbal, I., & Iqbal, K. (2007). Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration. Eur J Neurosci, 25(1), 59-68. https://doi.org/10.1111/j.1460-9568.2006.05226.x
Wegmann, S., Schöler, J., Bippes, C. A., Mandelkow, E., & Muller, D. J. (2011). Competing interactions stabilize pro- and anti-aggregant conformations of human Tau. J Biol Chem, 286(23), 20512-20524. https://doi.org/10.1074/jbc.M111.237875
Wiggin, G. R., Soloaga, A., Foster, J. M., Murray-Tait, V., Cohen, P., & Arthur, J. S. (2002). MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts. Mol Cell Biol, 22(8), 2871-2881. https://doi.org/10.1128/mcb.22.8.2871-2881.2002
Wille, H., Drewes, G., Biernat, J., Mandelkow, E. M., & Mandelkow, E. (1992). Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. J Cell Biol, 118(3), 573-584. https://doi.org/10.1083/jcb.118.3.573
Wiśniewski, H. M., Narang, H. K., & Terry, R. D. (1976). Neurofibrillary tangles of paired helical filaments. J Neurol Sci, 27(2), 173-181. https://doi.org/10.1016/0022-510x(76)90059-9
Won, J., & Silva, A. J. (2008). Molecular and cellular mechanisms of memory allocation in neuronetworks. Neurobiol Learn Mem, 89(3), 285-292. https://doi.org/10.1016/j.nlm.2007.08.017
Woo, N. H., Teng, H. K., Siao, C. J., Chiaruttini, C., Pang, P. T., Milner, T. A., Hempstead, B. L., & Lu, B. (2005). Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci, 8(8), 1069-1077. https://doi.org/10.1038/nn1510
Wu, J. W., Herman, M., Liu, L., Simoes, S., Acker, C. M., Figueroa, H., Steinberg, J. I., Margittai, M., Kayed, R., Zurzolo, C., Di Paolo, G., & Duff, K. E. (2013). Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J Biol Chem, 288(3), 1856-1870. https://doi.org/10.1074/jbc.M112.394528
Ye, C., Liang, Y., Chen, Y., Xiong, Y., She, Y., Zhong, X., Chen, H., & Huang, M. (2021). Berberine improves cognitive impairment by simultaneously impacting cerebral blood flow and β-amyloid accumulation in an APP/tau/PS1 mouse model of Alzheimer's disease. Cells, 10(5). https://doi.org/10.3390/cells10051161
Yoon, S. S., & Jo, S. A. (2012). Mechanisms of amyloid-β peptide clearance: Potential therapeutic targets for Alzheimer's disease. Biomol Ther (Seoul), 20(3), 245-255. https://doi.org/10.4062/biomolther.2012.20.3.245
Youdim, K. A., Qaiser, M. Z., Begley, D. J., Rice-Evans, C. A., & Abbott, N. J. (2004). Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med, 36(5), 592-604. https://doi.org/10.1016/j.freeradbiomed.2003.11.023
Yu, X., Luo, Y., Dinkel, P., Zheng, J., Wei, G., Margittai, M., Nussinov, R., & Ma, B. (2012). Cross-seeding and conformational selection between three- and four-repeat human Tau proteins. J Biol Chem, 287(18), 14950-14959. https://doi.org/10.1074/jbc.M112.340794
Yu, Y., Run, X., Liang, Z., Li, Y., Liu, F., Liu, Y., Iqbal, K., Grundke-Iqbal, I., & Gong, C. X. (2009). Developmental regulation of tau phosphorylation, tau kinases, and tau phosphatases. J Neurochem, 108(6), 1480-1494. https://doi.org/10.1111/j.1471-4159.2009.05882.x
Zeng, Y., Liu, Y., Wu, M., Liu, J., & Hu, Q. (2012). Activation of TrkB by 7,8-dihydroxyflavone prevents fear memory defects and facilitates amygdalar synaptic plasticity in aging. J Alzheimers Dis, 31(4), 765-778. https://doi.org/10.3233/jad-2012-120886
Zhang, Z., Liu, X., Schroeder, J. P., Chan, C. B., Song, M., Yu, S. P., Weinshenker, D., & Ye, K. (2014). 7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology, 39(3), 638-650. https://doi.org/10.1038/npp.2013.243
Zhong, Q., Congdon, E. E., Nagaraja, H. N., & Kuret, J. (2012). Tau isoform composition influences rate and extent of filament formation. J Biol Chem, 287(24), 20711-20719. https://doi.org/10.1074/jbc.M112.364067
Zhu, S., Shala, A., Bezginov, A., Sljoka, A., Audette, G., & Wilson, D. J. (2015). Hyperphosphorylation of intrinsically disordered tau protein induces an amyloidogenic shift in its conformational ensemble. PLoS One, 10(3), e0120416. https://doi.org/10.1371/journal.pone.0120416