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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Review Article

An Insight into the Protein Aggregation in Alzheimer’s Disease and its Inhibition

Author(s): Abdul Basit Khan and Rizwan Hasan Khan*

Volume 30, Issue 11, 2023

Published on: 10 November, 2023

Page: [900 - 912] Pages: 13

DOI: 10.2174/0109298665247757231020044633

Price: $65

Abstract

Alzheimer’s disease, a neurodegenerative disease, is a progressive and irreversible disease that has become a global challenge due to its increasing prevalence and absence of available potential therapies. Protein misfolding and aggregation are known to be the root of several protein neurodegenerative diseases, including Alzheimer’s disease. Protein aggregation is a phenomenon where misfolded proteins accumulate and clump together intra-or extracellularly. This accumulation of misfolded amyloid proteins leads to the formation of plaquesin the neuronal cells, also known as amyloid β plaques. The synthesis of amyloid β plaques and tau protein aggregation are the hallmarks of Alzheimer’s disease. Potential therapeutics must be developed in conjunction with an understanding of the possible root cause involving complex mechanisms. The development of therapeutics that can inhibit protein misfolding and aggregation, involved in the pathogenesis of Alzheimer's disease, could be one of the potential solutions to the disease.

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[1]
Khan, M.V.; Zakariya, S.M.; Khan, R.H. Protein folding, misfolding and aggregation: A tale of constructive to destructive assembly. Int. J. Biol. Macromol., 2018, 112, 217-229.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.099] [PMID: 29374532]
[2]
Hassan, M.N.; Nabi, F.; Khan, A.N.; Hussain, M.; Siddiqui, W.A.; Uversky, V.N.; Khan, R.H. The amyloid state of proteins: A boon or bane? Int. J. Biol. Macromol., 2022, 200, 593-617.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.01.115] [PMID: 35074333]
[3]
Sweeney, P.; Park, H.; Baumann, M.; Dunlop, J.; Frydman, J.; Kopito, R.; McCampbell, A.; Leblanc, G.; Venkateswaran, A.; Nurmi, A.; Hodgson, R. Protein misfolding in neurodegenerative diseases: Implications and strategies. Transl. Neurodegener., 2017, 6(1), 6.
[http://dx.doi.org/10.1186/s40035-017-0077-5] [PMID: 28293421]
[4]
Zaman, M.; Khan, A.N.; Uzzaman, W.; Zakariya, S.M.; Khan, R.H. Protein misfolding, aggregation and mechanism of amyloid cytotoxicity: An overview and therapeutic strategies to inhibit aggregation. Int. J. Biol. Macromol., 2019, 134, 1022-1037.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.05.109] [PMID: 31128177]
[5]
Zakariya, S.M.; Zehra, A.; Khan, R.H. Biophysical insight into protein folding, aggregate formation and its inhibition strategies. Protein Pept. Lett., 2022, 29(1), 22-36.
[http://dx.doi.org/10.2174/0929866528666211125114421] [PMID: 34823456]
[6]
Fan, L.; Mao, C.; Hu, X.; Zhang, S.; Yang, Z.; Hu, Z.; Sun, H.; Fan, Y.; Dong, Y.; Yang, J.; Shi, C.; Xu, Y. New Insights Into the Pathogenesis of Alzheimer’s Disease. Front. Neurol., 2020, 10, 1312.
[http://dx.doi.org/10.3389/fneur.2019.01312] [PMID: 31998208]
[7]
National Insitute on Aging. Alzheimer's Disease Fact Sheet. 2023. Available From: https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet
[8]
Palmqvist, S.; Janelidze, S.; Quiroz, Y.T.; Zetterberg, H.; Lopera, F.; Stomrud, E.; Su, Y.; Chen, Y.; Serrano, G.E.; Leuzy, A.; Mattsson-Carlgren, N.; Strandberg, O.; Smith, R.; Villegas, A.; Sepulveda-Falla, D.; Chai, X.; Proctor, N.K.; Beach, T.G.; Blennow, K.; Dage, J.L.; Reiman, E.M.; Hansson, O. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs Other Neurodegenerative Disorders. JAMA, 2020, 324(8), 772-781.
[http://dx.doi.org/10.1001/jama.2020.12134] [PMID: 32722745]
[9]
Tiwari, S.; Atluri, V.; Kaushik, A.; Yndart, A.; Nair, M. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. Int. J. Nanomed., 2019, 14, 5541-5554.
[http://dx.doi.org/10.2147/IJN.S200490] [PMID: 31410002]
[10]
Hartl, F.U. Protein misfolding diseases. Annu. Rev. Biochem., 2017, 86(1), 21-26.
[http://dx.doi.org/10.1146/annurev-biochem-061516-044518] [PMID: 28441058]
[11]
Murrell, J.; Farlow, M.; Ghetti, B.; Benson, M.D. A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science, 1991, 254(5028), 97-99.
[http://dx.doi.org/10.1126/science.1925564] [PMID: 1925564]
[12]
Parihar, M.S.; Hemnani, T. Alzheimer’s disease pathogenesis and therapeutic interventions. J. Clin. Neurosci., 2004, 11(5), 456-467.
[http://dx.doi.org/10.1016/j.jocn.2003.12.007] [PMID: 15177383]
[13]
Nie, Q.; Du, X.; Geng, M. Small molecule inhibitors of amyloid β peptide aggregation as a potential therapeutic strategy for Alzheimer’s disease. Acta Pharmacol. Sin., 2011, 32(5), 545-551.
[http://dx.doi.org/10.1038/aps.2011.14] [PMID: 21499284]
[14]
Francis, P.T.; Palmer, A.M.; Snape, M.; Wilcock, G.K. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J. Neurol. Neurosurg. Psychiatry, 1999, 66(2), 137-147.
[http://dx.doi.org/10.1136/jnnp.66.2.137] [PMID: 10071091]
[15]
Martorana, A.; Esposito, Z.; Koch, G. Beyond the cholinergic hypothesis: Do current drugs work in Alzheimer’s disease? CNS Neurosci. Ther., 2010, 16(4), no.
[http://dx.doi.org/10.1111/j.1755-5949.2010.00175.x] [PMID: 20560995]
[16]
Mohandas, E.; Rajmohan, V.; Raghunath, B. Neurobiology of Alzheimer′s disease. Indian J. Psychiatry, 2009, 51(1), 55-61.
[http://dx.doi.org/10.4103/0019-5545.44908] [PMID: 19742193]
[17]
Bekdash, R.A. The Cholinergic system, the adrenergic system and the neuropathology of Alzheimer’s disease. Int. J. Mol. Sci., 2021, 22(3), 1273.
[http://dx.doi.org/10.3390/ijms22031273] [PMID: 33525357]
[18]
Picciotto, M.R.; Higley, M.J.; Mineur, Y.S. Acetylcholine as a neuromodulator: Cholinergic signaling shapes nervous system function and behavior. Neuron, 2012, 76(1), 116-129.
[http://dx.doi.org/10.1016/j.neuron.2012.08.036] [PMID: 23040810]
[19]
Tiwari, P.; Dwivedi, S.; Singh, M.P.; Mishra, R.; Chandy, A. Basic and modern concepts on cholinergic receptor: A review. Asian Pacific J Trop Dis, 2013, 3(5), 413-420.
[20]
Tougu, V. Acetylcholinesterase: Mechanism of Catalysis and Inhibition. Curr. Med. Chem. Cent. Nerv. Syst. Agents, 2001, 1(2), 155-170.
[http://dx.doi.org/10.2174/1568015013358536]
[21]
García-Ayllón, M.S.; Small, D.H.; Avila, J.; Sáez-Valero, J. Revisiting the role of acetylcholinesterase in Alzheimer’s disease: Cross-talk with P-tau and β-amyloid. Front. Mol. Neurosci., 2011, 4, 22.
[http://dx.doi.org/10.3389/fnmol.2011.00022] [PMID: 21949503]
[22]
Lombardo, S. Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment. Neuropharmacology, 2015, 96, 255-262.
[http://dx.doi.org/10.1016/j.neuropharm.2014.11.018]
[23]
Talesa, V.N. Acetylcholinesterase in Alzheimer’s disease. Mech. Ageing Dev., 2001, 122(16), 1961-1969.
[http://dx.doi.org/10.1016/S0047-6374(01)00309-8] [PMID: 11589914]
[24]
Finder, V.H.; Glockshuber, R. Amyloid-β Aggregation. Neurodegener. Dis., 2007, 4(1), 13-27.
[http://dx.doi.org/10.1159/000100355] [PMID: 17429215]
[25]
Coburger, I.; Dahms, S.O.; Roeser, D.; Gührs, K.H.; Hortschansky, P.; Than, M.E. Analysis of the overall structure of the multi-domain amyloid precursor protein (APP). PLoS One, 2013, 8(12), e81926.
[http://dx.doi.org/10.1371/journal.pone.0081926] [PMID: 24324731]
[26]
Gralle, M.; Ferreira, S.T. Structure and functions of the human amyloid precursor protein: The whole is more than the sum of its parts. Prog. Neurobiol., 2007, 82(1), 11-32.
[http://dx.doi.org/10.1016/j.pneurobio.2007.02.001] [PMID: 17428603]
[27]
O’Brien, R.J.; Wong, P.C. Amyloid precursor protein processing and Alzheimer’s disease. Annu. Rev. Neurosci., 2011, 34(1), 185-204.
[http://dx.doi.org/10.1146/annurev-neuro-061010-113613] [PMID: 21456963]
[28]
Sadigh-Eteghad, S.; Sabermarouf, B.; Majdi, A.; Talebi, M.; Farhoudi, M.; Mahmoudi, J. Amyloid-beta: A crucial factor in Alzheimer’s disease. Med. Princ. Pract., 2015, 24(1), 1-10.
[http://dx.doi.org/10.1159/000369101] [PMID: 25471398]
[29]
Chow, V.W.; Mattson, M.P.; Wong, P.C.; Gleichmann, M. An overview of APP processing enzymes and products. Neuromolecular Med., 2010, 12(1), 1-12.
[http://dx.doi.org/10.1007/s12017-009-8104-z] [PMID: 20232515]
[30]
Venugopal, C.; Demos, C.; Jagannatha Rao, K.; Pappolla, M.; Sambamurti, K. Beta-secretase: Structure, function, and evolution. CNS Neurol. Disord. Drug Targets, 2008, 7(3), 278-294.
[http://dx.doi.org/10.2174/187152708784936626] [PMID: 18673212]
[31]
Wang, H.; Li, R.; Shen, Y. β-Secretase: Its biology as a therapeutic target in diseases. Trends Pharmacol. Sci., 2013, 34(4), 215-225.
[http://dx.doi.org/10.1016/j.tips.2013.01.008] [PMID: 23452816]
[32]
Murphy, M.P.; LeVine, H., III. Alzheimer’s disease and the amyloid-beta peptide. J. Alzheimers Dis., 2010, 19(1), 311-323.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[33]
Frozza, R.L.; Lourenco, M.V.; De Felice, F.G. Challenges for Alzheimer’s disease therapy: Insights from novel mechanisms beyond memory defects. Front. Neurosci., 2018, 12(37), 37.
[http://dx.doi.org/10.3389/fnins.2018.00037] [PMID: 29467605]
[34]
Selkoe, D.J.; Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med., 2016, 8(6), 595-608.
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[35]
Karve, S.J.; Ringman, J.M.; Lee, A.S.; Juarez, K.O.; Mendez, M.F. Comparison of clinical characteristics between familial and non-familial early onset Alzheimer’s disease. J. Neurol., 2012, 259(10), 2182-2188.
[http://dx.doi.org/10.1007/s00415-012-6481-y] [PMID: 22460587]
[36]
Bateman, R.J.; Aisen, P.S.; De Strooper, B.; Fox, N.C.; Lemere, C.A.; Ringman, J.M.; Salloway, S.; Sperling, R.A.; Windisch, M.; Xiong, C. Autosomal-dominant Alzheimer’s disease: A review and proposal for the prevention of Alzheimer’s disease. Alzheimers Res. Ther., 2010, 3(1), 1.
[http://dx.doi.org/10.1186/alzrt59] [PMID: 21211070]
[37]
Pflanzner, T.; Janko, M. C.; Andre-Dohmen, B.; Reuss, S.; Weggen, S.; Roebroek, A. J.; Kuhlmann, C. R. ALRP1 mediates bidirectional transcytosis of amyloid-β across the blood-brain barrier. Neurobiol Aging., 2011, 32(12), 2323.e1-11.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.05.025]
[38]
Jennifer, L. Neurodegenerative and movement disorders.In: Cerebrospinal Fluid in Clinical Practice; Duke University, 2009.
[http://dx.doi.org/10.1016/B978-141602908-3.50017-0]
[39]
Guo, T.; Zhang, D.; Zeng, Y. AMolecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Molecular Neurodeg, 2020, 15(40)
[http://dx.doi.org/10.1186/s13024-020-00391-7]
[40]
Findeis, M.A. The role of amyloid β peptide 42 in Alzheimer’s disease. Pharmacol. Ther., 2007, 116(2), 266-286.
[http://dx.doi.org/10.1016/j.pharmthera.2007.06.006] [PMID: 17716740]
[41]
Ball, K.A.; Phillips, A.H.; Wemmer, D.E.; Head-Gordon, T. Differences in β-strand populations of monomeric Aβ40 and Aβ42. Biophys. J., 2013, 104(12), 2714-2724.
[http://dx.doi.org/10.1016/j.bpj.2013.04.056] [PMID: 23790380]
[42]
Chen, Gf.; Xu, Th.; Yan, Y. Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacol. Sin., 2017, 38(9), 1205-1235.
[http://dx.doi.org/10.1038/aps.2017.28]
[43]
Harper, J. D. Mechanistic studies of beta protein amyloid formation in Alzheimer's disease: Identification and characterization of protofibril intermediates Semantic Scholar, 1998.
[44]
Goel, P.; Chakrabarti, S.; Goel, K.; Bhutani, K.; Chopra, T.; Bali, S. Neuronal cell death mechanisms in Alzheimer’s disease: An insight. Front. Mol. Neurosci., 2022, 15, 937133.
[http://dx.doi.org/10.3389/fnmol.2022.937133] [PMID: 36090249]
[45]
García-Osta, A.; Dong, J.; Moreno-Aliaga, M.J.; Ramirez, M.J. p27, the cell cycle and Alzheimer´s disease. Int. J. Mol. Sci., 2022, 23(3), 1211.
[http://dx.doi.org/10.3390/ijms23031211] [PMID: 35163135]
[46]
Sekine-Aizawa, Y.; Hama, E.; Watanabe, K.; Tsubuki, S.; Kanai-Azuma, M.; Kanai, Y.; Arai, H.; Aizawa, H.; Iwata, N.; Saido, T.C. Matrix metalloproteinase (MMP) system in brain: Identification and characterization of brain-specific MMP highly expressed in cerebellum. Eur. J. Neurosci., 2001, 13(5), 935-948.
[http://dx.doi.org/10.1046/j.0953-816x.2001.01462.x] [PMID: 11264666]
[47]
Willem, M.; Tahirovic, S.; Busche, M.A.; Ovsepian, S.V.; Chafai, M.; Kootar, S.; Hornburg, D.; Evans, L.D.B.; Moore, S.; Daria, A.; Hampel, H.; Müller, V.; Giudici, C.; Nuscher, B.; Wenninger-Weinzierl, A.; Kremmer, E.; Heneka, M.T.; Thal, D.R.; Giedraitis, V.; Lannfelt, L.; Müller, U.; Livesey, F.J.; Meissner, F.; Herms, J.; Konnerth, A.; Marie, H.; Haass, C. η-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature, 2015, 526(7573), 443-447.
[http://dx.doi.org/10.1038/nature14864] [PMID: 26322584]
[48]
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.https://doi.org/ARTN20410.3389/fnagi.2019.00204
[http://dx.doi.org/10.3389/fnagi.2019.00204] [PMID: 31447664]
[49]
Avila, J.; Lucas, J.J.; Pérez, M.; Hernández, F. Role of tau protein in both physiological and pathological conditions. Physiol. Rev., 2004, 84(2), 361-384.
[http://dx.doi.org/10.1152/physrev.00024.2003] [PMID: 15044677]
[50]
Gong, C.X.; Iqbal, K. Hyperphosphorylation of microtubule-associated protein tau: A promising therapeutic target for Alzheimer disease. Curr. Med. Chem., 2008, 15(23), 2321-2328.
[http://dx.doi.org/10.2174/092986708785909111] [PMID: 18855662]
[51]
Schoch, K.M.; DeVos, S.L.; Miller, R.L.; Chun, S.J.; Norrbom, M.; Wozniak, D.F.; Dawson, H.N.; Bennett, C.F.; Rigo, F.; Miller, T.M. Increased 4R-tau induces pathological changes in a human-tau mouse model. Neuron, 2016, 90(5), 941-947.
[http://dx.doi.org/10.1016/j.neuron.2016.04.042] [PMID: 27210553]
[52]
Billingsley, M.L.; Kincaid, R.L. Regulated phosphorylation and dephosphorylation of tau protein: Effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem. J., 1997, 323(3), 577-591.
[http://dx.doi.org/10.1042/bj3230577] [PMID: 9169588]
[53]
Briner, A.; Götz, J.; Polanco, J.C. Fyn kinase controls tau aggregation In Vivo. Cell Rep., 2020, 32(7), 108045.
[http://dx.doi.org/10.1016/j.celrep.2020.108045] [PMID: 32814048]
[54]
Pîrşcoveanu, D.F.V.; Pirici, I.; Tudorică, V.; Bălşeanu, T.A.; Albu, V.C.; Bondari, S.; Bumbea, A.M.; Pîrşcoveanu, M. Tau protein in neurodegenerative diseases - a review. Rom. J. Morphol. Embryol., 2017, 58(4), 1141-1150.
[PMID: 29556602]
[55]
Anand, R.; Gill, K. D.; Mahdi, A. A. Therapeutics of Alzheimer's disease: Past, present and future. Neuropharmacol., 2014, 76(Pt A), 27-50.
[http://dx.doi.org/10.1016/j.neuropharm.2013.07.004]
[56]
Götz, J.; Halliday, G.; Nisbet, R.M. Molecular pathogenesis of the tauopathies. Annu. Rev. Pathol., 2019, 14(1), 239-261.
[http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012936] [PMID: 30355155]
[57]
Pooler, A.M.; Polydoro, M.; Wegmann, S. Propagation of tau pathology in Alzheimer's disease: Identification of novel therapeutic targets. Alzheimers Res Ther., 2013, 5(5), 49.
[http://dx.doi.org/10.1186/alzrt214]
[58]
Chen, X.Q.; Mobley, W.C. Alzheimer disease pathogenesis: Insights from molecular and cellular biology studies of oligomeric Aβ and tau species. Front. Neurosci., 2019, 13(659), 659.
[http://dx.doi.org/10.3389/fnins.2019.00659] [PMID: 31293377]
[59]
Luan, K.; Rosales, J.L.; Lee, K.Y. Viewpoint: Crosstalks between neurofibrillary tangles and amyloid plaque formation. Ageing Res. Rev., 2013, 12(1), 174-181.
[http://dx.doi.org/10.1016/j.arr.2012.06.002] [PMID: 22728532]
[60]
Wu, H.Y.; Kuo, P.C.; Wang, Y.T.; Lin, H.T.; Roe, A.D.; Wang, B.Y.; Han, C.L.; Hyman, B.T.; Chen, Y.J.; Tai, H.C. β-amyloid induces pathology-related patterns of tau hyperphosphorylation at synaptic terminals. J. Neuropathol. Exp. Neurol., 2018, 77(9), 814-826.
[http://dx.doi.org/10.1093/jnen/nly059] [PMID: 30016458]
[61]
Muralidar, S.; Ambi, S.V.; Sekaran, S.; Thirumalai, D.; Palaniappan, B. Role of tau protein in Alzheimer’s disease: The prime pathological player. Int. J. Biol. Macromol., 2020, 163, 1599-1617.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.07.327] [PMID: 32784025]
[62]
Barracchia, C.G.; Tira, R.; Parolini, F.; Munari, F.; Bubacco, L.; Spyroulias, G.A.; D’Onofrio, M.; Assfalg, M. Unsaturated fatty acid-induced conformational transitions and aggregation of the repeat domain of tau. Molecules, 2020, 25(11), 2716.
[http://dx.doi.org/10.3390/molecules25112716] [PMID: 32545360]
[63]
Arboleda-Velasquez, J.F.; Lopera, F.; O’Hare, M.; Delgado-Tirado, S.; Marino, C.; Chmielewska, N.; Saez-Torres, K.L.; Amarnani, D.; Schultz, A.P.; Sperling, R.A.; Leyton-Cifuentes, D.; Chen, K.; Baena, A.; Aguillon, D.; Rios-Romenets, S.; Giraldo, M.; Guzmán-Vélez, E.; Norton, D.J.; Pardilla-Delgado, E.; Artola, A.; Sanchez, J.S.; Acosta-Uribe, J.; Lalli, M.; Kosik, K.S.; Huentelman, M.J.; Zetterberg, H.; Blennow, K.; Reiman, R.A.; Luo, J.; Chen, Y.; Thiyyagura, P.; Su, Y.; Jun, G.R.; Naymik, M.; Gai, X.; Bootwalla, M.; Ji, J.; Shen, L.; Miller, J.B.; Kim, L.A.; Tariot, P.N.; Johnson, K.A.; Reiman, E.M.; Quiroz, Y.T. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: A case report. Nat. Med., 2019, 25(11), 1680-1683.
[http://dx.doi.org/10.1038/s41591-019-0611-3] [PMID: 31686034]
[64]
Arnsten, A.F.T.; Datta, D.; Del Tredici, K.; Braak, H. Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer’s disease. Alzheimers Dement., 2021, 17(1), 115-124.
[http://dx.doi.org/10.1002/alz.12192] [PMID: 33075193]
[65]
Busche, M.A.; Wegmann, S.; Dujardin, S. Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in Vivo. Nat. Neurosci., 2019, 22(1), 75-64.
[http://dx.doi.org/10.1038/s41593-018-0289-8]
[66]
Haass, C.; Mandelkow, E. Fyn-tau-amyloid: A toxic triad. Cell, 2010, 142(3), 356-358.
[http://dx.doi.org/10.1016/j.cell.2010.07.032] [PMID: 20691893]
[67]
Tang, S.J.; Fesharaki-Zadeh, A.; Takahashi, H.; Nies, S.H.; Smith, L.M.; Luo, A.; Chyung, A.; Chiasseu, M.; Strittmatter, S.M. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathol. Commun., 2020, 8(1), 96.
[http://dx.doi.org/10.1186/s40478-020-00976-9] [PMID: 32611392]
[68]
Cataldi, R.; Chia, S.; Pisani, K.; Ruggeri, F.S.; Xu, C.K.; Šneideris, T.; Perni, M.; Sarwat, S.; Joshi, P.; Kumita, J.R.; Linse, S.; Habchi, J.; Knowles, T.P.J.; Mannini, B.; Dobson, C.M.; Vendruscolo, M. A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers. Commun. Biol., 2021, 4(1), 19.
[http://dx.doi.org/10.1038/s42003-020-01490-3] [PMID: 33398040]
[69]
Hamley, I.W. The amyloid beta peptide: A chemist’s perspective. Role in Alzheimer’s and fibrillization. Chem. Rev., 2012, 112(10), 5147-5192.
[http://dx.doi.org/10.1021/cr3000994] [PMID: 22813427]
[70]
Ashrafian, H.; Zadeh, E.H.; Khan, R.H. Review on Alzheimer’s disease: Inhibition of amyloid beta and tau tangle formation. Int. J. Biol. Macromol., 2021, 167, 382-394.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.11.192] [PMID: 33278431]
[71]
Wang, Q.; Yu, X.; Li, L.; Zheng, J. Inhibition of amyloid-β aggregation in Alzheimer’s disease. Curr. Pharm. Des., 2014, 20(8), 1223-1243.
[http://dx.doi.org/10.2174/13816128113199990068] [PMID: 23713775]
[72]
Robinson, M.; Lou, J.; Mehrazma, B.; Rauk, A.; Beazely, M.; Leonenko, Z. Pseudopeptide amyloid aggregation inhibitors: In silico, single molecule and cell viability studies. Int. J. Mol. Sci., 2021, 22(3), 1051.
[http://dx.doi.org/10.3390/ijms22031051] [PMID: 33494369]
[73]
van Dyck, C.H. Anti-amyloid-β monoclonal antibodies for Alzheimer’s disease: Pitfalls and promise. Biol. Psychiatry, 2018, 83(4), 311-319.
[http://dx.doi.org/10.1016/j.biopsych.2017.08.010] [PMID: 28967385]
[74]
Montoliu-Gaya, L.; Villegas, S. A β -Immunotherapeutic strategies: A wide range of approaches for Alzheimer’s disease treatment. Expert Rev. Mol. Med., 2016, 18, e13.
[http://dx.doi.org/10.1017/erm.2016.11] [PMID: 27357999]
[75]
Ariga, T.; Miyatake, T.; Yu, R.K. Role of proteoglycans and glycosaminoglycans in the pathogenesis of Alzheimer’s disease and related disorders: Amyloidogenesis and therapeutic strategies-A review. J. Neurosci. Res., 2010, 88(11), 2303-2315.
[http://dx.doi.org/10.1002/jnr.22393] [PMID: 20623617]
[76]
Folch, J.; Petrov, D.; Ettcheto, M.; Abad, S.; Sánchez-López, E.; García, M.L.; Olloquequi, J.; Beas-Zarate, C.; Auladell, C.; Camins, A. Current research therapeutic strategies for Alzheimer’s disease treatment. Neural Plast., 2016, 2016, 1-15.
[http://dx.doi.org/10.1155/2016/8501693] [PMID: 26881137]
[77]
Vassar, R. BACE1 inhibition as a therapeutic strategy for Alzheimer’s disease. J. Sport Health Sci., 2016, 5(4), 388-390.
[http://dx.doi.org/10.1016/j.jshs.2016.10.004] [PMID: 30356583]
[78]
Das, B.; Yan, R. A close look at BACE1 inhibitors for Alzheimer’s disease treatment. CNS Drugs, 2019, 33(3), 251-263.
[http://dx.doi.org/10.1007/s40263-019-00613-7] [PMID: 30830576]
[79]
Lee, J.H.; Ahn, N.H.; Choi, S.B.; Kwon, Y.; Yang, S.H. Natural products targeting amyloid beta in Alzheimer’s disease. Int. J. Mol. Sci., 2021, 22(5), 2341.
[http://dx.doi.org/10.3390/ijms22052341] [PMID: 33652858]
[80]
Zhenxia, Z.; Min, L.; Peikui, Y.; Zikai, C.; Yaqun, L.; Junli, W.; Fenlian, Y.; Yuzhong, Z. Inhibition of tau aggregation and associated cytotoxicity on neuron-like cells by calycosin. Int. J. Biol. Macromol., 2021, 171, 74-81.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.12.030] [PMID: 33301850]
[81]
Desale, S.E.; Dubey, T.; Chinnathambi, S. α-Linolenic acid inhibits Tau aggregation and modulates Tau conformation. Int. J. Biol. Macromol., 2021, 166, 687-693.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.10.226] [PMID: 33130263]
[82]
Xiao, S.; Lu, Y.; Wu, Q.; Yang, J.; Chen, J.; Zhong, S.; Eliezer, D.; Tan, Q.; Wu, C. Fisetin inhibits tau aggregation by interacting with the protein and preventing the formation of β-strands. Int. J. Biol. Macromol., 2021, 178, 381-393.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.210] [PMID: 33662414]
[83]
Kim, H.; Park, B.S.; Lee, K.G.; Choi, C.Y.; Jang, S.S.; Kim, Y.H.; Lee, S.E. Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. J. Agric. Food Chem., 2005, 53(22), 8537-8541.
[http://dx.doi.org/10.1021/jf051985c] [PMID: 16248550]
[84]
Zhang, L.; Wang, H.; Zhou, Y.; Zhu, Y.; Fei, M. Fisetin alleviates oxidative stress after traumatic brain injury via the Nrf2-ARE pathway. Neurochem. Int., 2018, 118, 304-313.
[http://dx.doi.org/10.1016/j.neuint.2018.05.011] [PMID: 29792955]
[85]
Noble, W.; Hanger, D.P.; Miller, C.C.J.; Lovestone, S. The importance of tau phosphorylation for neurodegenerative diseases. Front. Neurol., 2013, 4, 83.
[http://dx.doi.org/10.3389/fneur.2013.00083] [PMID: 23847585]
[86]
Llorens-Martín, M.; Jurado, J.; Hernández, F.; Avila, J. GSK-3β, a pivotal kinase in Alzheimer disease. Front. Mol. Neurosci., 2014, 7, 46.
[http://dx.doi.org/10.3389/fnmol.2014.00046] [PMID: 24904272]
[87]
Dewachter, I.; Ris, L.; Jaworski, T.; Seymour, C.M.; Kremer, A.; Borghgraef, P.; De Vijver, H.; Godaux, E.; Van Leuven, F. GSK3ß, a centre-staged kinase in neuropsychiatric disorders, modulates long term memory by inhibitory phosphorylation at Serine-9. Neurobiol. Dis., 2009, 35(2), 193-200.
[http://dx.doi.org/10.1016/j.nbd.2009.04.003] [PMID: 19379814]
[88]
Zhang, F.; Zhong, R.; Cheng, C.; Li, S.; Le, W. New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease. Acta Pharmacol. Sin., 2021, 42(9), 1382-1389.
[http://dx.doi.org/10.1038/s41401-020-00565-5] [PMID: 33268824]
[89]
Chakraborty, S.; Rakshit, J.; Bandyopadhyay, J.; Basu, S. Multi-target inhibition ability of neohesperidin dictates its neuroprotective activity: Implication in Alzheimer’s disease therapeutics. Int. J. Biol. Macromol., 2021, 176, 315-324.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.073] [PMID: 33581209]
[90]
Long, J.M.; Holtzman, D.M. Alzheimer disease: An update on pathobiology and treatment strategies. Cell, 2019, 179(2), 312-339.
[http://dx.doi.org/10.1016/j.cell.2019.09.001] [PMID: 31564456]
[91]
Congdon, E.E.; Wu, J.W.; Myeku, N.; Figueroa, Y.H.; Herman, M.; Marinec, P.S.; Gestwicki, J.E.; Dickey, C.A.; Yu, W.H.; Duff, K.E. Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy, 2012, 8(4), 609-622.
[http://dx.doi.org/10.4161/auto.19048] [PMID: 22361619]
[92]
Serenó, L.; Coma, M.; Rodríguez, M.; Sánchez-Ferrer, P.; Sánchez, M.B.; Gich, I.; Agulló, J.M.; Pérez, M.; Avila, J.; Guardia-Laguarta, C.; Clarimón, J.; Lleó, A.; Gómez-Isla, T. A novel GSK-3β inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol. Dis., 2009, 35(3), 359-367.
[http://dx.doi.org/10.1016/j.nbd.2009.05.025] [PMID: 19523516]
[93]
Noble, W.; Jimenez-Sanchez, M.; Perez-Nievas, B.G.; Hanger, D.P. Considerations for future tau-targeted therapeutics: Can they deliver? Expert Opin. Drug Discov., 2020, 15(3), 265-267.
[http://dx.doi.org/10.1080/17460441.2020.1685977] [PMID: 31661994]
[94]
Budd Haeberlein, S.; Aisen, P.; Barkhof, F. Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease. J Prev Alzheimer's Dis, 2020, 9, 197-210.
[http://dx.doi.org/10.14283/jpad.2022.30]
[95]
Ebell, M.H.; Barry, H.C. Why physicians should not prescribe aducanumab for Alzheimer disease. Am. Fam. Physician, 2022, 105(4), 353-354.
[PMID: 35426626]
[96]
Planche, V.; Villain, N. US food and drug administration approval of aducanumab—is amyloid load a valid surrogate end point for Alzheimer disease clinical trials? JAMA Neurol., 2021, 78(11), 1307-1308.
[http://dx.doi.org/10.1001/jamaneurol.2021.3126] [PMID: 34515750]
[97]
Khan, A.N.; Nabi, F.; Ajmal, M.R.; Ali, S.M.; Almutairi, F.M.; Alalawy, A.I.; Khan, R.H. Moxifloxacin disrupts and attenuates Aβ42 Fibril and oligomer formation: Plausibly repositioning an antibiotic as therapeutic against Alzheimer’s disease. ACS Chem. Neurosci., 2022, 13(16), 2529-2539.
[http://dx.doi.org/10.1021/acschemneuro.2c00371] [PMID: 35930676]
[98]
Cummings, J.; Lee, G.; Nahed, P.; Kambar, M.E.Z.N.; Zhong, K.; Fonseca, J.; Taghva, K. Alzheimer’s disease drug development pipeline Alzheimers Dement. (N. Y.), 2022, 8(1), e12295.
[http://dx.doi.org/10.1002/trc2.12295] [PMID: 35516416]
[99]
Srivastava, S.; Ahmad, R.; Khare, S.K. Alzheimer’s disease and its treatment by different approaches: A review. Eur. J. Med. Chem., 2021, 216, 113320.
[http://dx.doi.org/10.1016/j.ejmech.2021.113320] [PMID: 33652356]
[100]
Sergeant, N.; Vingtdeux, V.; Eddarkaoui, S.; Gay, M.; Evrard, C.; Le Fur, N.; Laurent, C.; Caillierez, R.; Obriot, H.; Larchanché, P.E.; Farce, A.; Coevoet, M.; Carato, P.; Kouach, M.; Descat, A.; Dallemagne, P.; Buée-Scherrer, V.; Blum, D.; Hamdane, M.; Buée, L.; Melnyk, P. New piperazine multi-effect drugs prevent neurofibrillary degeneration and amyloid deposition, and preserve memory in animal models of Alzheimer’s disease. Neurobiol. Dis., 2019, 129, 217-233.
[http://dx.doi.org/10.1016/j.nbd.2019.03.028] [PMID: 30928644]
[101]
Imbimbo, B.P.; Ippati, S.; Watling, M.; Balducci, C. Accelerating Alzheimer’s disease drug discovery and development: What’s the way forward? Expert Opin. Drug Discov., 2021, 16(7), 727-735.
[http://dx.doi.org/10.1080/17460441.2021.1887132] [PMID: 33653187]
[102]
Gklinos, P.; Papadopoulou, M.; Stanulovic, V.; Mitsikostas, D.D.; Papadopoulos, D. Monoclonal antibodies as neurological therapeutics. Pharmaceuticals (Basel), 2021, 14(2), 92.
[http://dx.doi.org/10.3390/ph14020092] [PMID: 33530460]
[103]
Kioussis, B.; Tuttle, C.S.L.; Heard, D.S.; Kennedy, B.K.; Lautenschlager, N.T.; Maier, A.B. Targeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review. Ageing Res. Rev., 2021, 67, 101302.
[http://dx.doi.org/10.1016/j.arr.2021.101302] [PMID: 33609776]
[104]
Yu, T.W.; Lane, H.Y.; Lin, C.H. Novel therapeutic approaches for Alzheimer’s disease: An updated review. Int. J. Mol. Sci., 2021, 22(15), 8208.
[http://dx.doi.org/10.3390/ijms22158208] [PMID: 34360973]
[105]
Yang, Y.; Tapias, V.; Acosta, D.; Xu, H.; Chen, H.; Bhawal, R.; Anderson, E.T.; Ivanova, E.; Lin, H.; Sagdullaev, B.T.; Chen, J.; Klein, W.L.; Viola, K.L.; Gandy, S.; Haroutunian, V.; Beal, M.F.; Eliezer, D.; Zhang, S.; Gibson, G.E. Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease. Nat. Commun., 2022, 13(1), 159.
[http://dx.doi.org/10.1038/s41467-021-27572-2] [PMID: 35013160]
[106]
Ma, X.; Li, H.; He, Y.; Hao, J. The emerging link between O-GlcNAcylation and neurological disorders. Cell. Mol. Life Sci., 2017, 74(20), 3667-3686.
[http://dx.doi.org/10.1007/s00018-017-2542-9] [PMID: 28534084]
[107]
Dyer, R.R.; Ford, K.I.; Robinson, R.A.S. The roles of S-nitrosylation and S-glutathionylation in Alzheimer’s disease. Methods Enzymol., 2019, 626, 499-538.
[http://dx.doi.org/10.1016/bs.mie.2019.08.004] [PMID: 31606089]
[108]
De Plano, L.M.; Calabrese, G.; Conoci, S.; Guglielmino, S.P.P.; Oddo, S.; Caccamo, A. Applications of CRISPR-Cas9 in Alzheimer’s disease and related disorders. Int. J. Mol. Sci., 2022, 23(15), 8714.
[http://dx.doi.org/10.3390/ijms23158714] [PMID: 35955847]
[109]
Khan, A. N.; Khan, R. H. Protein misfolding and related human diseases: A comprehensive review of toxicity, proteins involved, and current therapeutic strategies. Int J Biol Macromol., 2022, 223(Pt A), 143-160.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.11.031]
[110]
Lei, P.; Ayton, S.; Bush, A.I. The essential elements of Alzheimer’s disease. J. Biol. Chem., 2020, 296, 100105.
[http://dx.doi.org/10.1074/jbc.REV120.008207] [PMID: 33219130]
[111]
Gupta, J.; Fatima, M.T.; Islam, Z.; Khan, R.H.; Uversky, V.N.; Salahuddin, P. Nanoparticle formulations in the diagnosis and therapy of Alzheimer’s disease. Int. J. Biol. Macromol., 2019, 130, 515-526.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.02.156] [PMID: 30826404]
[112]
Roberts, K.F.; Brue, C.R.; Preston, A.; Baxter, D.; Herzog, E.; Varelas, E.; Meade, T.J. Cobalt(III) Schiff base complexes stabilize non-fibrillar amyloid-β aggregates with reduced toxicity. J. Inorg. Biochem., 2020, 213, 111265.
[http://dx.doi.org/10.1016/j.jinorgbio.2020.111265] [PMID: 33059154]
[113]
Windsor, P.K.; Plassmeyer, S.P.; Mattock, D.S.; Bradfield, J.C.; Choi, E.Y.; Miller, B.R., III; Han, B.H. Biflavonoid-induced disruption of hydrogen bonds leads to amyloid-β disaggregation. Int. J. Mol. Sci., 2021, 22(6), 2888.
[http://dx.doi.org/10.3390/ijms22062888] [PMID: 33809196]
[114]
Ganesh, R.; Kannan, I. Molecular docking study of certain plant alkaloid derivatives as inhibitors of various drug targets of Alzheimer’s disease. Biomed. Pharmacol. J., 2017, 10(3), 1489-1494.
[http://dx.doi.org/10.13005/bpj/1257]
[115]
Jokar, S.; Erfani, M.; Bavi, O.; Khazaei, S.; Sharifzadeh, M.; Hajiramezanali, M.; Beiki, D.; Shamloo, A. Design of peptide-based inhibitor agent against amyloid-β aggregation: Molecular docking, synthesis and in vitro evaluation. Bioorg. Chem., 2020, 102, 104050.
[http://dx.doi.org/10.1016/j.bioorg.2020.104050] [PMID: 32663672]
[116]
Busche, M.A.; Hyman, B.T. Synergy between amyloid-β and tau in Alzheimer's disease. Nat Neurosci., 2020, 23(10), 1183-1193.
[http://dx.doi.org/10.1038/s41593-020-0687-6]
[117]
Zetterberg, H.; Bendlin, B.B. Biomarkers for Alzheimer's disease-preparing for a new era of disease-modifying therapies. Mol Psychiatry., 2021, 26(1), 296-306.
[http://dx.doi.org/10.1038/s41380-020-0721-9]
[118]
Trejo-Lopez, J.A.; Yachnis, A.T.; Prokop, S. Neuropathology of Alzheimer's disease. Neurotherapeutics, 2022, 19(1), 173-185.
[http://dx.doi.org/10.1007/s13311-021-01146-y]

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