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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease

Author(s): Md. Sahab Uddin*, Abdullah Al Mamun, Md. Ataur Rahman, Tapan Behl, Asma Perveen, Abdul Hafeez, May N. Bin-Jumah, Mohamed M. Abdel-Daim and Ghulam Md Ashraf*

Volume 20 , Issue 26 , 2020

Page: [2380 - 2390] Pages: 11

DOI: 10.2174/1568026620666200601161703

Price: $65


Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated neurotoxicity in AD.

Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded, as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of their proper clearance could result in amyloid disease including AD. The neuropathological changes of AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood until now.

Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to uncover the molecular etiologies behind the complicated AD pathogenesis.

Keywords: , Tau, Protein misfolding, Protein interaction, Neurotoxicity, Alzheimer's disease.

Graphical Abstract
Cooper, G.M.; Hausman, R.E. The Cell: A Molecular Approach, 7th ed; Sinauer Associates: London, 2015.
Ashraf, G.M.; Greig, N.H.; Khan, T.A.; Hassan, I.; Tabrez, S.; Shakil, S.; Sheikh, I.A.; Zaidi, S.K.; Akram, M.; Jabir, N.R.; Firoz, C.K.; Naeem, A.; Alhazza, I.M.; Damanhouri, G.A.; Kamal, M.A. Protein misfolding and aggregation in Alzheimer’s disease and type 2 diabetes mellitus. CNS Neurol. Disord. Drug Targets, 2014, 13(7), 1280-1293.
[ ] [PMID: 25230234]
Ciechanover, A.; Kwon, Y.T. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp. Mol. Med., 2015, 47 e147
[ ] [PMID: 25766616]
Mirza, Z.; Ali, A.; Ashraf, G.M.; Kamal, M.A.; Abuzenadah, A.M.; Choudhary, A.G.; Damanhouri, G.A.; Sheikh, I.A. Proteomics approaches to understand linkage between Alzheimer’s disease and type 2 diabetes mellitus. CNS Neurol. Disord. Drug Targets, 2014, 13(2), 213-225.
[ ] [PMID: 24059316]
Uddin, M.S.; Kabir, M.T.; Tewari, D.; Mathew, B.; Aleya, L. Emerging signal regulating potential of small molecule biflavonoids to combat neuropathological insults of Alzheimer’s disease. Sci. Total Environ., 2020, 700 134836
[ ] [PMID: 31704512]
Kabir, M.T.; Uddin, M.S.; Begum, M.M.; Thangapandiyan, S.; Rahman, M.S.; Aleya, L.; Mathew, B.; Ahmed, M.; Barreto, G.E.; Ashraf, G.M. Cholinesterase inhibitors for Alzheimer’s disease: multitargeting strategy based on anti-Alzheimer’s drugs repositioning. Curr. Pharm. Des., 2019, 25(33), 3519-3535.
[ ] [PMID: 31593530]
Mathew, B.; Parambi, D.G.T.; Mathew, G.E.; Uddin, M.S.; Inasu, S.T.; Kim, H.; Marathakam, A.; Unnikrishnan, M.K.; Carradori, S. Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer’s and Parkinson’s diseases. Arch. Pharm. (Weinheim), 2019, 352(11) e1900177
[ ] [PMID: 31478569]
Uddin, M.S.; Mamun, A.A.; Jakaria, M.; Thangapandiyan, S.; Ahmad, J.; Rahman, M.A.; Mathew, B.; Abdel-Daim, M.M.; Aleya, L. Emerging promise of sulforaphane-mediated Nrf2 signaling cascade against neurological disorders. Sci. Total Environ., 2020, 707 135624
[ ] [PMID: 31784171]
Al Mamun, A.; Uddin, M.S. KDS2010: A potent highly selective and reversible mao-b inhibitor to abate Alzheimer’s disease. Comb. Chem. High Throughput Screen., 2020, 23. (ePub ahead of print)
[] [PMID: 31957612]
Fiszer, A.; Ellison-Klimontowicz, M.E.; Krzyzosiak, W.J. Silencing of genes responsible for polyQ diseases using chemically modified single-stranded siRNAs. Acta Biochim. Pol., 2016, 63(4), 759-764.
[PMID: 27770571]
Mamun, A.A.; Uddin, M.S.; Mathew, B.; Ashraf, G.M. Toxic tau: structural origins of tau aggregation in Alzheimer’s disease. Neural Regen. Res., 2020, 15(8), 1417-1420.
[ ] [PMID: 31997800]
Rahman, M.A.; Rahman, M.R.; Zaman, T.; Uddin, M.S.; Islam, R.; Abdel-Daim, M.M.; Rhim, H. Emerging potential of naturally occurring autophagy modulators against neurodegeneration. Curr. Pharm. Des., 2020, 26(7), 772-779.
[ ] [PMID: 31914904]
Serpell, L.C.; Smith, J.M. Direct visualisation of the β-sheet structure of synthetic Alzheimer’s amyloid. J. Mol. Biol., 2000, 299(1), 225-231.
[ ] [PMID: 10860734]
Haass, C.; Kaether, C.; Thinakaran, G.; Sisodia, S. Trafficking and proteolytic processing of APP. Cold Spring Harb. Perspect. Med., 2012, 2(5) a006270
[ ] [PMID: 22553493]
Kabir, M.T.; Sufian, M.A.; Uddin, M.S.; Begum, M.M.; Akhter, S.; Islam, A.; Mathew, B.; Islam, M.S.; Amran, M.S.; Md Ashraf, G. NMDA receptor antagonists: repositioning of memantine as a multitargeting agent for Alzheimer’s therapy. Curr. Pharm. Des., 2019, 25(33), 3506-3518.
[ ] [PMID: 31604413]
Larson, M.E.; Lesné, S.E. Soluble Aβ oligomer production and toxicity. J. Neurochem., 2012, 120(Suppl. 1), 125-139.
[ ] [PMID: 22121920]
Esparza, T.J.; Wildburger, N.C.; Jiang, H.; Gangolli, M.; Cairns, N.J.; Bateman, R.J.; Brody, D.L. Soluble amyloid-beta aggregates from human Alzheimer’s disease brains. Sci. Rep., 2016, 6, 38187.
[ ] [PMID: 27917876]
Aliev, G.; Ashraf, G.M.; Kaminsky, Y.G.; Sheikh, I.A.; Sudakov, S.K.; Yakhno, N.N.; Benberin, V.V.; Bachurin, S.O. Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease. Am. J. Alzheimers Dis. Other Demen., 2013, 28(7), 660-670.
[ ] [PMID: 24085255]
Sahab Uddin, M.; Ashraf, Md. Introductory chapter: Alzheimer’s disease. The most common cause of dementia. Advances in Dementia Research; IntechOpen: London, 2019.
Islam, M.S.; Kanak, F.; Iqbal, M.A.; Islam, K.F.; Al Mamun, A.; Uddin, M.S. Analyzing the Status of the Autism Spectrum Disorder amid Children with Intellectual Disabilities in Bangladesh. Biomed. Pharmacol. J., 2018, 11, 689-701.
Harilal, S.; Jose, J.; Parambi, D.G.T.; Kumar, R.; Mathew, G.E.; Uddin, M.S.; Kim, H.; Mathew, B. Advancements in nanotherapeutics for Alzheimer’s disease: current perspectives. J. Pharm. Pharmacol., 2019, 71(9), 1370-1383.
[ ] [PMID: 31304982]
Uddin, M.S.; Tewari, D.; Mamun, A.A.; Kabir, M.T.; Niaz, K.; Wahed, M.I.I.; Barreto, G.E.; Ashraf, G.M. Circadian and sleep dysfunction in Alzheimer’s disease. Ageing Res. Rev., 2020, 60 101046
[ ] [PMID: 32171783]
Uddin, M.S.; Kabir, M.T.; Mamun, A.A.; Barreto, G.E.; Rashid, M.; Perveen, A.; Ashraf, G.M. Pharmacological approaches to mitigate neuroinflammation in Alzheimer’s disease. Int. Immunopharmacol., 2020, 84 106479
[ ] [PMID: 32353686]
Uddin, M.S.; Kabir, M.T.; Tewari, D.; Al Mamun, A.; Mathew, B.; Aleya, L.; Barreto, G.E.; Bin-Jumah, M.N.; Abdel-Daim, M.M.; Ashraf, G.M. Revisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer’s disease. J. Neurol. Sci., 2020, 116974
Hossain, M.F.; Uddin, M.S.; Uddin, G.M.S.; Sumsuzzman, D.M.; Islam, M.S.; Barreto, G.E.; Mathew, B.; Ashraf, G.M. Melatonin in Alzheimer’s disease: a latent endogenous regulator of neurogenesis to mitigate Alzheimer’s neuropathology. Mol. Neurobiol., 2019, 56(12), 8255-8276.
[ ] [PMID: 31209782]
Uddin, M.S.; Al Mamun, A.; Kabir, M.T.; Jakaria, M.; Mathew, B.; Barreto, G.E.; Ashraf, G.M. Nootropic and anti-Alzheimer’s actions of medicinal plants: molecular insight into therapeutic potential to alleviate Alzheimer’s neuropathology. Mol. Neurobiol., 2019, 56(7), 4925-4944.
[ ] [PMID: 30414087]
Al Mamun, A.; Uddin, M.S.; Kabir, M.T.; Khanum, S.; Sarwar, M.S.; Mathew, B.; Rauf, A.; Ahmed, M.; Ashraf, G.M. Exploring the promise of targeting ubiquitin-proteasome system to combat Alzheimer’s disease. Neurotox. Res., 2020, 38, 8-17.
[ ] [PMID: 32157628 ]
Clayton, K.A.; Van Enoo, A.A.; Ikezu, T. Alzheimer’s disease: The role of microglia in brain homeostasis and proteopathy. Front. Neurosci., 2017, 11, 680.
[ ] [PMID: 29311768]
Uddin, M.S.; Kabir, M.T.; Jakaria, M.; Sobarzo-Sánchez, E.; Barreto, G.E.; Perveen, A.; Hafeez, A.; Bin-Jumah, M.N.; Abdel-Daim, M.M.; Ashraf, G.M. Exploring the potential of neuroproteomics in Alzheimer's disease., Curr. Top. Med. Chem., 2020, 20. (ePub ahead of print).
[] [PMID: 32493192]
Gouras, G.K. Aging, metabolism, synaptic activity, and Aβ in Alzheimer’s Disease. Front. Aging Neurosci., 2019, 11, 185.
[ ] [PMID: 31396077]
Wildburger, N.C.; Esparza, T.J.; LeDuc, R.D.; Fellers, R.T.; Thomas, P.M.; Cairns, N.J.; Kelleher, N.L.; Bateman, R.J.; Brody, D.L. Diversity of amyloid-beta proteoforms in the Alzheimer’s disease brain. Sci. Rep., 2017, 7(1), 9520.
[ ] [PMID: 28842697]
Uddin, M.S.; Stachowiak, A.; Mamun, A.A.; Tzvetkov, N.T.; Takeda, S.; Atanasov, A.G.; Bergantin, L.B.; Abdel-Daim, M.M.; Stankiewicz, A.M. Autophagy and Alzheimer’s disease: from molecular mechanisms to therapeutic implications., Front. Aging Neurosci., 2018, 10, 04.
[] [PMID: 29441009]
Uddin, M.S.; Kabir, M.T.; Rahman, M.M.; Mathew, B.; Shah, M.A.; Ashraf, G.M. TV 3326 for Alzheimer’s dementia: a novel multimodal che and mao inhibitors to mitigate Alzheimer’s‐like neuropathology. J. Pharm. Pharmacol., 2020, 38, 8-17.
Uddin, M.S.; Kabir, M.T.; Jeandet, P.; Mathew, B.; Ashraf, G.M.; Perveen, A.; Bin-Jumah, M.N.; Mousa, S.A.; Abdel-Daim, M.M. Novel anti-Alzheimer’s therapeutic molecules targeting amyloid precursor protein processing. Oxid. Med. Cell. Longev., 2020, 2020 7039138
Pereira, C.; Santos, M.S.; Oliveira, C. Mitochondrial function impairment induced by amyloid β-peptide on PC12 cells. Neuroreport, 1998, 9(8), 1749-1755.
[ ] [PMID: 9665595]
Hartmann, T.; Bieger, S.C.; Brühl, B.; Tienari, P.J.; Ida, N.; Allsop, D.; Roberts, G.W.; Masters, C.L.; Dotti, C.G.; Unsicker, K.; Beyreuther, K. Distinct sites of intracellular production for Alzheimer’s disease A β40/42 amyloid peptides. Nat. Med., 1997, 3(9), 1016-1020.
[ ] [PMID: 9288729]
Lathia, J.D.; Okun, E.; Tang, S.C.; Griffioen, K.; Cheng, A.; Mughal, M.R.; Laryea, G.; Selvaraj, P.K. ffrench-Constant, C.; Magnus, T.; Arumugam, T.V.; Mattson, M.P. Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation. J. Neurosci., 2008, 28(51), 13978-13984.
[ ] [PMID: 19091986]
Uddin, M.S.; Kabir, M.T. Emerging signal regulating potential of genistein against Alzheimer’s disease: a promising molecule of interest. Front. Cell Dev. Biol., 2019, 7, 197.
[ ] [PMID: 31620438]
Dobson, C.M. Getting out of shape. Nature, 2002, 418(6899), 729-730.
[ ] [PMID: 12181546]
Kirkitadze, M.D.; Condron, M.M.; Teplow, D.B. Identification and characterization of key kinetic intermediates in amyloid β-protein fibrillogenesis. J. Mol. Biol., 2001, 312(5), 1103-1119.
[ ] [PMID: 11580253]
Dobson, C.M. Protein misfolding, evolution and disease. Trends Biochem. Sci., 1999, 24(9), 329-332.
[ ] [PMID: 10470028]
Dobson, C.M. Protein folding and misfolding. Nature, 2003, 426(6968), 884-890.
[ ] [PMID: 14685248]
Taylor, J.P.; Hardy, J.; Fischbeck, K.H. Toxic proteins in neurodegenerative disease. Science, 2002, 296(5575), 1991-1995.
[ ] [PMID: 12065827]
Celej, M.S.; Sarroukh, R.; Goormaghtigh, E.; Fidelio, G.D.; Ruysschaert, J.M.; Raussens, V. Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure. Biochem. J., 2012, 443(3), 719-726.
[ ] [PMID: 22316405]
Cerf, E.; Sarroukh, R.; Tamamizu-Kato, S.; Breydo, L.; Derclaye, S.; Dufrêne, Y.F.; Narayanaswami, V.; Goormaghtigh, E.; Ruysschaert, J.M.; Raussens, V. Antiparallel β-sheet: a signature structure of the oligomeric amyloid β-peptide. Biochem. J., 2009, 421(3), 415-423.
[ ] [PMID: 19435461]
Uddin, M.S.; Rahman, M.M.; Jakaria, M.; Rahman, M.S.; Hossain, M.S.; Islam, A.; Ahmed, M.; Mathew, B.; Omar, U.M.; Barreto, G.E.; Ashraf, G.M. Estrogen signaling in Alzheimer’s disease: molecular insights and therapeutic targets for Alzheimer’s dementia. Mol. Neurobiol., 2020, 57, 2654-2670.
[ ] [PMID: 32297302]
Cerf, A.; Molnár, G.; Vieu, C. Novel approach for the assembly of highly efficient SERS substrates. ACS Appl. Mater. Interfaces, 2009, 1(11), 2544-2550.
[ ] [PMID: 20356125]
Teplow, D.B.; Lazo, N.D.; Bitan, G.; Bernstein, S.; Wyttenbach, T.; Bowers, M.T.; Baumketner, A.; Shea, J.E.; Urbanc, B.; Cruz, L.; Borreguero, J.; Stanley, H.E. Elucidating amyloid β-protein folding and assembly: A multidisciplinary approach. Acc. Chem. Res., 2006, 39(9), 635-645.
[ ] [PMID: 16981680]
Ding, Y.; Ortelli, F.; Rossiter, L.C.; Hemingway, J.; Ranson, H. The Anopheles gambiae glutathione transferase supergene family: annotation, phylogeny and expression profiles. BMC Genomics, 2003, 4(1), 35.
[ ] [PMID: 12914673]
George, A.R.; Howlett, D.R. Computationally derived structural models of the β-amyloid found in Alzheimer’s disease plaques and the interaction with possible aggregation inhibitors. Biopolymers, 1999, 50(7), 733-741.
[<733:AID-BIP6>3.0.CO;2-7 ] [PMID: 10547528]
Lin, L.; Faraco, J.; Li, R.; Kadotani, H.; Rogers, W.; Lin, X.; Qiu, X.; de Jong, P.J.; Nishino, S.; Mignot, E. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell, 1999, 98(3), 365-376.
[ ] [PMID: 10458611]
Tjernberg, L.O.; Callaway, D.J.E.; Tjernberg, A.; Hahne, S.; Lilliehöök, C.; Terenius, L.; Thyberg, J.; Nordstedt, C. A molecular model of Alzheimer amyloid β-peptide fibril formation. J. Biol. Chem., 1999, 274(18), 12619-12625.
[ ] [PMID: 10212241]
Lazo, N.D.; Downing, D.T. Amyloid fibrils may be assembled from β-helical protofibrils. Biochemistry, 1998, 37(7), 1731-1735.
[ ] [PMID: 9492738]
Sawaya, M.R.; Sambashivan, S.; Nelson, R.; Ivanova, M.I.; Sievers, S.A.; Apostol, M.I.; Thompson, M.J.; Balbirnie, M.; Wiltzius, J.J.W.; McFarlane, H.T.; Madsen, A.Ø.; Riekel, C.; Eisenberg, D. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature, 2007, 447(7143), 453-457.
[ ] [PMID: 17468747]
Balbach, J.J.; Ishii, Y.; Antzutkin, O.N.; Leapman, R.D.; Rizzo, N.W.; Dyda, F.; Reed, J.; Tycko, R. Amyloid fibril formation by A β 16-22, a seven-residue fragment of the Alzheimer’s β-amyloid peptide, and structural characterization by solid state NMR. Biochemistry, 2000, 39(45), 13748-13759.
[ ] [PMID: 11076514]
Oddo, S.; Caccamo, A.; Tran, L.; Lambert, M.P.; Glabe, C.G.; Klein, W.L.; LaFerla, F.M. Temporal profile of amyloid-β (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology. J. Biol. Chem., 2006, 281(3), 1599-1604.
[ ] [PMID: 16282321]
Lacor, P.N.; Buniel, M.C.; Chang, L.; Fernandez, S.J.; Gong, Y.; Viola, K.L.; Lambert, M.P.; Velasco, P.T.; Bigio, E.H.; Finch, C.E.; Krafft, G.A.; Klein, W.L. Synaptic targeting by Alzheimer’s-related amyloid β oligomers. J. Neurosci., 2004, 24(45), 10191-10200.
[ ] [PMID: 15537891]
Swerdlow, R.H. Pathogenesis of Alzheimer’s disease. Clin. Interv. Aging, 2007, 2(3), 347-359.
[PMID: 18044185]
Palop, J.J.; Mucke, L. Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat. Neurosci., 2010, 13(7), 812-818.
[ ] [PMID: 20581818]
Yuan, A.; Rao, M.V. Veeranna; Nixon, R.A. Neurofilaments at a glance. J. Cell Sci., 2012, 125(Pt 14), 3257-3263.
[ ] [PMID: 22956720]
Liu, Y.L.; Guo, Y.S.; Xu, L.; Wu, S.Y.; Wu, D.X.; Yang, C.; Zhang, Y.; Li, C.Y. Alternation of neurofilaments in immune-mediated injury of spinal cord motor neurons. Spinal Cord, 2009, 47(2), 166-170.
[ ] [PMID: 18663372]
Munoz, D.G.; Greene, C.; Perl, D.P.; Selkoe, D.J. Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients. J. Neuropathol. Exp. Neurol., 1988, 47(1), 9-18.
[ ] [PMID: 3334727]
Ashton, N.J.; Leuzy, A.; Lim, Y.M.; Troakes, C.; Hortobágyi, T.; Höglund, K.; Aarsland, D.; Lovestone, S.; Schöll, M.; Blennow, K.; Zetterberg, H.; Hye, A. Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration. Acta Neuropathol. Commun., 2019, 7(1), 5.
[ ] [PMID: 30626432]
Uddin, M.S.; Mamun, A.A.; Labu, Z.K.; Hidalgo-Lanussa, O.; Barreto, G.E.; Ashraf, G.M. Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis. J. Cell. Physiol., 2019, 234(6), 8094-8112.
[ ] [PMID: 30362531]
Uddin, M.S.; Kabir, M.T.; Rahman, M.H.; Alim, M.A.; Rahman, M.M.; Khatkar, A.; Al Mamun, A.; Rauf, A.; Mathew, B.; Ashraf, G.M. Exploring the multifunctional neuroprotective promise of rasagiline derivatives for multi-dysfunctional Alzheimer’s disease. Curr. Pharm. Des., 2020, 26. (ePub ahead of Print)
[PMID: 32250219]
Kabir, M.T.; Uddin, M.S.; Mathew, B.; Das, P.K.; Ashraf, G.M.; Ashraf, G.M. Emerging promise of immunotherapy for Alzheimer’s disease: a new hope for the development of Alzheimer’s vaccine. Curr. Top. Med. Chem., 2020, 20, 1214-1234.
[ ] [PMID: 32321405]
Iqbal, K.; Wisniewski, H.M.; Grundke-Iqbal, I.; Korthals, J.K.; Terry, R.D. Chemical pathology of neurofibrils. Neurofibrillary tangles of Alzheimer’s presenile-senile dementia. J. Histochem. Cytochem., 1975, 23(7), 563-569.
[ ] [PMID: 1141687]
Uddin, M.S.; Kabir, M.T.; Niaz, K.; Jeandet, P.; Clément, C.; Mathew, B.; Rauf, A.; Rengasamy, K.R.R.; Sobarzo-Sánchez, E.; Ashraf, G.M.; Aleya, L. Molecular insight into the therapeutic promise of flavonoids against Alzheimer’s disease. Molecules, 2020, 25(6), 1267.
[ ] [PMID: 32168835]
Spires-Jones, T.L.; Stoothoff, W.H.; de Calignon, A.; Jones, P.B.; Hyman, B.T. Tau pathophysiology in neurodegeneration: a tangled issue. Trends Neurosci., 2009, 32(3), 150-159.
[ ] [PMID: 19162340]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science, 2002, 297, 353-356.
Uddin, M.S.; Kabir, M.T.; Al Mamun, A.; Abdel-Daim, M.M.; Barreto, G.E.; Ashraf, G.M. APOE and Alzheimer’s disease: evidence mounts that targeting apoe4 may combat Alzheimer’s pathogenesis. Mol. Neurobiol., 2019, 56(4), 2450-2465.
[ ] [PMID: 30032423]
Gandy, S.; Heppner, F.L. Breaking up (amyloid) is hard to do. PLoS Med., 2005, 2(12) e417
[ ] [PMID: 16363913]
Reynaud, E. Protein Misfolding and Degenerative Diseases. New Educator, 2010, 3, 28.
Giménez-Llort, L.; Blázquez, G.; Cañete, T.; Johansson, B.; Oddo, S.; Tobeña, A.; LaFerla, F.M.; Fernández-Teruel, A. Modeling behavioral and neuronal symptoms of Alzheimer’s disease in mice: a role for intraneuronal amyloid. Neurosci. Biobehav. Rev., 2007, 31(1), 125-147.
[ ] [PMID: 17055579]
Li, M.; Chen, L.; Lee, D.H.S.; Yu, L.C.; Zhang, Y. The role of intracellular amyloid β in Alzheimer’s disease. Prog. Neurobiol., 2007, 83(3), 131-139.
[ ] [PMID: 17889422]
Gouras, G.K.; Tampellini, D.; Takahashi, R.H.; Capetillo-Zarate, E. Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta Neuropathol., 2010, 119(5), 523-541.
[ ] [PMID: 20354705]
Bayer, T.A.; Wirths, O. Intracellular accumulation of amyloid-Beta - a predictor for synaptic dysfunction and neuron loss in Alzheimer’s disease. Front. Aging Neurosci., 2010, 2, 8.
[ ] [PMID: 20552046]
Jelinek, R. Lipids and Cellular Membranes in Amyloid Diseases; Wiley: New York, 2011.
Claeysen, S.; Cochet, M.; Donneger, R.; Dumuis, A.; Bockaert, J.; Giannoni, P. Alzheimer culprits: cellular crossroads and interplay. Cell. Signal., 2012, 24(9), 1831-1840.
[ ] [PMID: 22627093]
Burgos, P.V.; Mardones, G.A.; Rojas, A.L.; daSilva, L.L.P.; Prabhu, Y.; Hurley, J.H.; Bonifacino, J.S. Sorting of the Alzheimer’s disease amyloid precursor protein mediated by the AP-4 complex. Dev. Cell, 2010, 18(3), 425-436.
[ ] [PMID: 20230749]
Nixon, R.A. Autophagy in neurodegenerative disease: friend, foe or turncoat? Trends Neurosci., 2006, 29(9), 528-535.
[ ] [PMID: 16859759]
LaFerla, F.M.; Troncoso, J.C.; Strickland, D.K.; Kawas, C.H.; Jay, G. Neuronal cell death in Alzheimer’s disease correlates with apoE uptake and intracellular Abeta stabilization. J. Clin. Invest., 1997, 100(2), 310-320.
[ ] [PMID: 9218507]
D’Andrea, M.R.; Nagele, R.G.; Wang, H.Y.; Peterson, P.A.; Lee, D.H.S. Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer’s disease. Histopathology, 2001, 38(2), 120-134.
[ ] [PMID: 11207825]
Nagele, R.G.; D’Andrea, M.R.; Anderson, W.J.; Wang, H.Y. Intracellular accumulation of β-amyloid(1-42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer’s disease. Neuroscience, 2002, 110(2), 199-211.
[ ] [PMID: 11958863]
Aho, L.; Pikkarainen, M.; Hiltunen, M.; Leinonen, V.; Alafuzoff, I. Immunohistochemical visualization of amyloid-β protein precursor and amyloid-β in extra- and intracellular compartments in the human brain. J. Alzheimers Dis., 2010, 20(4), 1015-1028.
[ ] [PMID: 20413866]
Posse De Chaves, E.; Mohamed, A. Aß Internalization by Neurons and Glia. Int. J. Alzheimers Dis., 2011, 2011, 1-17.
Lai, A.Y.; McLaurin, J. Mechanisms of amyloid-Beta Peptide uptake by neurons: the role of lipid rafts and lipid raft-associated proteins. Int. J. Alzheimers Dis., 2010, 2011 548380
[PMID: 21197446]
Wu, F.; Yao, P.J. Clathrin-mediated endocytosis and Alzheimer’s disease: an update. Ageing Res. Rev., 2009, 8(3), 147-149.
[ ] [PMID: 19491039]
Lopez, E.M.; Bell, K.F.S.; Ribeiro-da-Silva, A.; Cuello, A.C. Early changes in neurons of the hippocampus and neocortex in transgenic rats expressing intracellular human a-β. J. Alzheimers Dis., 2004, 6(4), 421-431.
[ ] [PMID: 15345813]
Gajdusek, D.C. Transmissible and non-transmissible amyloidoses: autocatalytic post-translational conversion of host precursor proteins to β-pleated sheet configurations. J. Neuroimmunol., 1988, 20(2-3), 95-110.
[ ] [PMID: 3143742]
Prusiner, S.B.; DeArmond, S.J. Prions causing nervous system degeneration. Lab. Invest., 1987, 56(4), 349-363.
[PMID: 2882063]
Glabe, C. Intracellular mechanisms of amyloid accumulation and pathogenesis in Alzheimer’s disease. J. Mol. Neurosci., 2001, 17(2), 137-145.
[ ] [PMID: 11816787]
Cataldo, A.M.; Hamilton, D.J.; Barnett, J.L.; Paskevich, P.A.; Nixon, R.A. Properties of the endosomal-lysosomal system in the human central nervous system: disturbances mark most neurons in populations at risk to degenerate in Alzheimer’s disease. J. Neurosci., 1996, 16(1), 186-199.
[ ] [PMID: 8613784]
Cataldo, A.M.; Peterhoff, C.M.; Troncoso, J.C.; Gomez-Isla, T.; Hyman, B.T.; Nixon, R.A. Endocytic pathway abnormalities precede amyloid β deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am. J. Pathol., 2000, 157(1), 277-286.
[ ] [PMID: 10880397]
Burdick, D.; Kosmoski, J.; Knauer, M.F.; Glabe, C.G. Preferential adsorption, internalization and resistance to degradation of the major isoform of the Alzheimer’s amyloid peptide, A beta 1-42, in differentiated PC12 cells. Brain Res., 1997, 746(1-2), 275-284.
[ ] [PMID: 9037507]
Ditaranto, K.; Tekirian, T.L.; Yang, A.J. Lysosomal membrane damage in soluble Abeta-mediated cell death in Alzheimer’s disease. Neurobiol. Dis., 2001, 8(1), 19-31.
[ ] [PMID: 11162237]
Guo, C.; Sun, L.; Chen, X.; Zhang, D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen. Res., 2013, 8(21), 2003-2014.
[PMID: 25206509]
Wang, X.; Wang, W.; Li, L.; Perry, G.; Lee, H.G.; Zhu, X. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim. Biophys. Acta, 2014, 1842(8), 1240-1247.
[ ] [PMID: 24189435]
Uddin, M.S.; Hossain, M.F.; Al Mamun, A.; Shah, M.A.; Hasana, S.; Bulbul, I.J.; Sarwar, M.S.; Mansouri, R.A.; Ashraf, G.M.; Rauf, A.; Abdel-Daim, M.M.; Bin-Jumah, M.N. Exploring the multimodal role of phytochemicals in the modulation of cellular signaling pathways to combat age-related neurodegeneration. Sci. Total Environ., 2020, 725 138313
Uddin, M.S.; Upaganlawar, A.B. Oxidative stress and antioxidant defense: biomedical value in health and diseases; Nova Science Publishers: New York, 2019.
Uddin, M.S.; Kabir, M.T. Oxidative stress in Alzheimer’s disease: molecular hallmarks of underlying vulnerability. In: Biological, Diagnostic and Therapeutic Advances in Alzheimer’s Disease; Springer: Singapore, 2019.
Lustbader, J.W.; Cirilli, M.; Lin, C.; Xu, H.W.; Takuma, K.; Wang, N.; Caspersen, C.; Chen, X.; Pollak, S.; Chaney, M.; Trinchese, F.; Liu, S.; Gunn-Moore, F.; Lue, L.F.; Walker, D.G.; Kappasamy, P.; Zewier, Z.L.; Arancio, O.; Stern, D.; Yan, S.S. Du, ; Wu, H. Directly links Aβ to mitochondrial toxicity in Alzheimer’s Disease Science, 2004, 304, 448-452.
Caspersen, C.; Wang, N.; Yao, J.; Sosunov, A.; Chen, X.; Lustbader, J.W.; Xu, H.W.; Stern, D.; McKhann, G.; Yan, S.D. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. FASEB J., 2005, 19(14), 2040-2041.
[ ] [PMID: 16210396]
Lin, M.T.; Beal, M.F. Alzheimer’s APP mangles mitochondria. Nat. Med., 2006, 12(11), 1241-1243.
[ ] [PMID: 17088888]
Hansson Petersen, C.A.; Alikhani, N.; Behbahani, H.; Wiehager, B.; Pavlov, P.F.; Alafuzoff, I.; Leinonen, V.; Ito, A.; Winblad, B.; Glaser, E.; Ankarcrona, M. The amyloid β-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc. Natl. Acad. Sci. USA, 2008, 105(35), 13145-13150.
[ ] [PMID: 18757748]
Yan, Y.; Liu, Y.; Sorci, M.; Belfort, G.; Lustbader, J.W.; Yan, S.S.; Wang, C. Surface plasmon resonance and nuclear magnetic resonance studies of ABAD-Abeta interaction. Biochemistry, 2007, 46(7), 1724-1731.
[ ] [PMID: 17253767]
Gillardon, F.; Rist, W.; Kussmaul, L.; Vogel, J.; Berg, M.; Danzer, K.; Kraut, N.; Hengerer, B. Proteomic and functional alterations in brain mitochondria from Tg2576 mice occur before amyloid plaque deposition. Proteomics, 2007, 7(4), 605-616.
[ ] [PMID: 17309106]
Crouch, P.J.; Blake, R.; Duce, J.A.; Ciccotosto, G.D.; Li, Q.X.; Barnham, K.J.; Curtain, C.C.; Cherny, R.A.; Cappai, R.; Dyrks, T.; Masters, C.L.; Trounce, I.A. Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42. J. Neurosci., 2005, 25(3), 672-679.
[ ] [PMID: 15659604]
Rhein, V.; Song, X.; Wiesner, A.; Ittner, L.M.; Baysang, G.; Meier, F.; Ozmen, L.; Bluethmann, H.; Dröse, S.; Brandt, U.; Savaskan, E.; Czech, C.; Götz, J.; Eckert, A. Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice. Proc. Natl. Acad. Sci. USA, 2009, 106(47), 20057-20062.
[ ] [PMID: 19897719]
Schwarz, D.S.; Blower, M.D. The endoplasmic reticulum: structure, function and response to cellular signaling. Cell. Mol. Life Sci., 2016, 73(1), 79-94.
[ ] [PMID: 26433683]
Wu, Y.; Whiteus, C.; Xu, C.S.; Hayworth, K.J.; Weinberg, R.J.; Hess, H.F.; De Camilli, P. Contacts between the endoplasmic reticulum and other membranes in neurons. Proc. Natl. Acad. Sci. USA, 2017, 114(24), E4859-E4867.
[ ] [PMID: 28559323]
Xu, C.; Bailly-Maitre, B.; Reed, J.C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest., 2005, 115(10), 2656-2664.
[ ] [PMID: 16200199]
Uddin, M.S.; Tewari, D.; Sharma, G.; Kabir, M.T.; Barreto, G.E.; Bin-Jumah, M.N.; Perveen, A.; Abdel-Daim, M.M.; Ashraf, G.M. Molecular mechanisms of ER stress and UPR in the pathogenesis of Alzheimer's disease., Mol. Neurobiol., 2020. (ePub ahead of print).
[] [PMID: 32430843]
Sahab Uddin, M.; Ashraf, G.M. Quality Control of Cellular Protein in Neurodegenerative Disorders; IGI Global: Hershey, 2020.
Cook, D.G.; Forman, M.S.; Sung, J.C.; Leight, S.; Kolson, D.L.; Iwatsubo, T.; Lee, V.M.Y.; Doms, R.W. Alzheimer’s A β(1-42) is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells. Nat. Med., 1997, 3(9), 1021-1023.
[ ] [PMID: 9288730]
Hoshino, T.; Nakaya, T.; Araki, W.; Suzuki, K.; Suzuki, T.; Mizushima, T. Endoplasmic reticulum chaperones inhibit the production of amyloid-β peptides. Biochem. J., 2007, 402(3), 581-589.
[ ] [PMID: 17132139]
Manzoni, C.; Colombo, L.; Bigini, P.; Diana, V.; Cagnotto, A.; Messa, M.; Lupi, M.; Bonetto, V.; Pignataro, M.; Airoldi, C.; Sironi, E.; Williams, A.; Salmona, M. The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. PLoS One, 2011, 6(9) e24909
[ ] [PMID: 21966382]
Földi, I.; Datki, Z.L.; Szabó, Z.; Bozsó, Z.; Penke, B.; Janáky, T. Proteomic study of the toxic effect of oligomeric Aβ1-42 in situ prepared from ‘iso-Aβ1-42’. J. Neurochem., 2011, 117(4), 691-702.
[ ] [PMID: 21388376]
Bückig, A.; Tikkanen, R.; Herzog, V.; Schmitz, A. Cytosolic and nuclear aggregation of the amyloid β-peptide following its expression in the endoplasmic reticulum. Histochem. Cell Biol., 2002, 118(5), 353-360.
[ ] [PMID: 12432446]
Ohyagi, Y.; Asahara, H.; Chui, D.H.; Tsuruta, Y.; Sakae, N.; Miyoshi, K.; Yamada, T.; Kikuchi, H.; Taniwaki, T.; Murai, H.; Ikezoe, K.; Furuya, H.; Kawarabayashi, T.; Shoji, M.; Checler, F.; Iwaki, T.; Makifuchi, T.; Takeda, K.; Kira, J.; Tabira, T. Intracellular Abeta42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer’s disease. FASEB J., 2005, 19(2), 255-257.
[ ] [PMID: 15548589]
Stewart, K.L.; Radford, S.E. Amyloid plaques beyond Aβ: a survey of the diverse modulators of amyloid aggregation. Biophys. Rev., 2017, 9(4), 405-419.
[ ] [PMID: 28631243]
Bondarev, S.A.; Antonets, K.S.; Kajava, A.V.; Nizhnikov, A.A.; Zhouravleva, G.A. Protein co-aggregation related to amyloids: methods of investigation, diversity, and classification. Int. J. Mol. Sci., 2018, 19(8), 2292.
[ ] [PMID: 30081572]
Chen, G.F.; Xu, T.H.; Yan, Y.; Zhou, Y.R.; Jiang, Y.; Melcher, K.; Xu, H.E. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol. Sin., 2017, 38(9), 1205-1235.
[ ] [PMID: 28713158]
Virok, D.P.; Simon, D.; Bozsó, Z.; Rajkó, R.; Datki, Z.; Bálint, É.; Szegedi, V.; Janáky, T.; Penke, B.; Fülöp, L. Protein array based interactome analysis of amyloid-β indicates an inhibition of protein translation. J. Proteome Res., 2011, 10(4), 1538-1547.
[ ] [PMID: 21244100]
Stiess, M.; Bradke, F. Neuronal transport: myosins pull the ER. Nat. Cell Biol., 2011, 13(1), 10-11.
[ ] [PMID: 21151133]
Oláh, J.; Vincze, O.; Virók, D.; Simon, D.; Bozsó, Z.; Tõkési, N.; Horváth, I.; Hlavanda, E.; Kovács, J.; Magyar, A.; Szũcs, M.; Orosz, F.; Penke, B.; Ovádi, J. Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. J. Biol. Chem., 2011, 286(39), 34088-34100.
[ ] [PMID: 21832049]
Juhász, G.; Földi, I.; Penke, B. Systems biology of Alzheimer’s disease: how diverse molecular changes result in memory impairment in AD. Neurochem. Int., 2011, 58(7), 739-750.
[ ] [PMID: 21333708]
Verdier, Y.; Földi, I.; Sergeant, N.; Fülöp, L.; Penke, Z.; Janáky, T.; Szücs, M.; Penke, B. Characterization of the interaction between Abeta 1-42 and glyceraldehyde phosphodehydrogenase. J. Pept. Sci., 2008, 14(6), 755-762.
[ ] [PMID: 18219703]
Guo, T.; Noble, W.; Hanger, D.P. Roles of tau protein in health and disease. Acta Neuropathol., 2017, 133(5), 665-704.
[ ] [PMID: 28386764]
Barbier, P.; Zejneli, O.; Martinho, M.; Lasorsa, A.; Belle, V.; Smet-Nocca, C.; Tsvetkov, P.O.; Devred, F.; Landrieu, I. Role of tau as a microtubule-associated protein: structural and functional aspects. Front. Aging Neurosci., 2019, 11, 204.
[ ] [PMID: 31447664]
Amadoro, G.; Corsetti, V.; Ciotti, M.T.; Florenzano, F.; Capsoni, S.; Amato, G.; Calissano, P. Endogenous Aβ causes cell death via early tau hyperphosphorylation. Neurobiol. Aging, 2011, 32(6), 969-990.
[ ] [PMID: 19628305]
Vossel, K.A.; Zhang, K.; Brodbeck, J.; Daub, A.C.; Sharma, P.; Finkbeiner, S.; Cui, B.; Mucke, L. Tau reduction prevents Abeta-induced defects in axonal transport. Science, 2010, 330(6001), 198.
[ ] [PMID: 20829454]
Fein, J.A.; Sokolow, S.; Miller, C.A.; Vinters, H.V.; Yang, F.; Cole, G.M.; Gylys, K.H. Co-localization of amyloid beta and tau pathology in Alzheimer’s disease synaptosomes. Am. J. Pathol., 2008, 172(6), 1683-1692.
[ ] [PMID: 18467692]
Takahashi, R.H.; Capetillo-Zarate, E.; Lin, M.T.; Milner, T.A.; Gouras, G.K. Co-occurrence of Alzheimer’s disease ß-amyloid and τ pathologies at synapses. Neurobiol. Aging, 2010, 31(7), 1145-1152.
[ ] [PMID: 18771816]
Du, H.; Guo, L.; Yan, S.; Sosunov, A.A.; McKhann, G.M.; Yan, S.S. Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proc. Natl. Acad. Sci. USA, 2010, 107(43), 18670-18675.
[ ] [PMID: 20937894]
Su, B.; Wang, X.; Lee, H.G.; Tabaton, M.; Perry, G.; Smith, M.A.; Zhu, X. Chronic oxidative stress causes increased tau phosphorylation in M17 neuroblastoma cells. Neurosci. Lett., 2010, 468(3), 267-271.
[ ] [PMID: 19914335]
Korff, A.; Liu, C.; Ginghina, C.; Shi, M.; Zhang, J. Alzheimer’s Disease Neuroimaging Initiative. α-Synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J. Alzheimers Dis., 2013, 36(4), 679-688.
[ ] [PMID: 23603399]
Hashiguchi, M.; Hashiguchi, T. Kinase-kinase interaction and modulation of tau phosphorylation. In: International Review of Cell and Molecular Biology; Elsevier Inc.: Amsterdam, 2013, Vol. 300, pp. 121-160.
Kawakami, F.; Suzuki, M.; Shimada, N.; Kagiya, G.; Ohta, E.; Tamura, K.; Maruyama, H.; Ichikawa, T. Stimulatory effect of α-synuclein on the tau-phosphorylation by GSK-3β. FEBS J., 2011, 278(24), 4895-4904.
[ ] [PMID: 21985244]
Kimura, T.; Tsutsumi, K.; Taoka, M.; Saito, T.; Masuda-Suzukake, M.; Ishiguro, K.; Plattner, F.; Uchida, T.; Isobe, T.; Hasegawa, M.; Hisanaga, S. Isomerase Pin1 stimulates dephosphorylation of tau protein at cyclin-dependent kinase (Cdk5)-dependent Alzheimer phosphorylation sites. J. Biol. Chem., 2013, 288(11), 7968-7977.
[ ] [PMID: 23362255]
Lim, J.; Balastik, M.; Lee, T.H.; Nakamura, K.; Liou, Y.C.; Sun, A.; Finn, G.; Pastorino, L.; Lee, V.M.Y.; Lu, K.P. Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy. J. Clin. Invest., 2008, 118(5), 1877-1889.
[ ] [PMID: 18431510]
Yotsumoto, K.; Saito, T.; Asada, A.; Oikawa, T.; Kimura, T.; Uchida, C.; Ishiguro, K.; Uchida, T.; Hasegawa, M.; Hisanaga, S. Effect of Pin1 or microtubule binding on dephosphorylation of FTDP-17 mutant Tau. J. Biol. Chem., 2009, 284(25), 16840-16847.
[ ] [PMID: 19401603]
Williamson, R.; Usardi, A.; Hanger, D.P.; Anderton, B.H. Membrane-bound β-amyloid oligomers are recruited into lipid rafts by a fyn-dependent mechanism. FASEB J., 2008, 22(5), 1552-1559.
[ ] [PMID: 18096814]
Roberson, E.D.; Halabisky, B.; Yoo, J.W.; Yao, J.; Chin, J.; Yan, F.; Wu, T.; Hamto, P.; Devidze, N.; Yu, G.Q.; Palop, J.J.; Noebels, J.L.; Mucke, L. Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer’s disease. J. Neurosci., 2011, 31(2), 700-711.
[ ] [PMID: 21228179]
Ittner, L.M.; Ke, Y.D.; Delerue, F.; Bi, M.; Gladbach, A.; van Eersel, J.; Wölfing, H.; Chieng, B.C.; Christie, M.J.; Napier, I.A.; Eckert, A.; Staufenbiel, M.; Hardeman, E.; Götz, J. Dendritic function of tau mediates amyloid-β toxicity in Alzheimer’s disease mouse models. Cell, 2010, 142(3), 387-397.
[ ] [PMID: 20655099]
Hernandez, P.; Lee, G.; Sjoberg, M.; MacCioni, R.B. Tau Phosphorylation by Cdk5 and fyn in response to amyloid peptide Aβ25-35. Involvement of Lipid Rafts. J. Alzheimer’s Dis., 2009, 16, 149-156.
[PMID: 19158430]
Scales, T.M.E.; Derkinderen, P.; Leung, K.Y.; Byers, H.L.; Ward, M.A.; Price, C.; Bird, I.N.; Perera, T.; Kellie, S.; Williamson, R.; Anderton, B.H.; Reynolds, C.H. Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn. Mol. Neurodegener., 2011, 6, 12.
[ ] [PMID: 21269457]
Bhaskar, K.; Hobbs, G.A.; Yen, S.H.; Lee, G. Tyrosine phosphorylation of tau accompanies disease progression in transgenic mouse models of tauopathy. Neuropathol. Appl. Neurobiol., 2010, 36(6), 462-477.
[ ] [PMID: 20609109]
Lee, G.; Thangavel, R.; Sharma, V.M.; Litersky, J.M.; Bhaskar, K.; Fang, S.M.; Do, L.H.; Andreadis, A.; Van Hoesen, G.; Ksiezak-Reding, H. Phosphorylation of tau by fyn: implications for Alzheimer’s disease. J. Neurosci., 2004, 24(9), 2304-2312.
[ ] [PMID: 14999081]

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