Inhibition of secretase: A promising technique for Alzheimer’s disease patients
DOI:
https://doi.org/10.70035/ijarts.2023.2131-35Keywords:
Alzheimer’s disease, Neurofibrillary tangles, Aβ plaque, Amyloid Precursor Protein, β Secretase, γ secretaseAbstract
Alzheimer’s is a globally known neurodegenerative disease. Aβ is a cleavage product of the 695-770 amino acid, single mem-brane-spanning protein known as the Aβ-precursor protein (APP), which is highly expressed in the nervous system. The most abundantly produced isoform of A by neurons is A40, while A42 has two C-terminal hydrophobic residues that increase its propensity to self-assemble into amyloid. As a consequence, despite differences in the relative numbers of plaques stained for A40 and A42, more plaques are immunoreactive for A42 than for A40. In addition to plaques and amyloid angiopathy, Aβ multimerizes into a range of oligomeric species that can interact with cells and impact brain function. Because all established risk factors for AD enhance its quantity and/or inclination to aggregate, A has taken on a key role in Alzheimer research. The Aβ plaque formation and hyperphosphorylation of Tau protein are key hallmarks of this disease. The maturation of Aβ occurred by two golden enzymes β secretase and γ secretase. In this review we discuss about some strategies which suppress these enzymes for prevention of Aβ plaque formation.
References
References
Ferri CP., Prince M., Brayne C., Brodaty H., Fratiglioni L., Ganguli M., Hall K., Hasegawa K., Hendrie H., Huang Y., Jorm A., Mathers C., Menezes PR., Rimmer E. and Scazufca M. 2005 Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 366(9503): 2112-2117. DOI: 10.1016/S0140-6736(05)67889-0.
Alzheimer's Disease International. 2018 World Alzheimer Report 2018 (cited 30 September 2018). https://www.alz.co.uk/research/world-report2018.
Viswanathan A. and Greenberg SM. 2011 Cerebral amyloid angiopathy in the elderly. Ann. Neurol. 70(6): 871–80. https://doi.org/10.1002/ana.22516.
Nilsson P., Iwata N., Muramatsu SI., Tjernberg LO., Winblad B. and Saido TC. 2010 Gene therapy in Alzheimer’s disease–potential for disease modification. J. cell. and molecule. Medi. 14(4): 741-757. doi:10.1111/j.1582-4934.2010.01038.x.
Scheltens P., Blennow K., Breteler MM., de Strooper B., Frisoni GB., Salloway S. and Van der Flier WM. 2016 Alzheimer's disease. Lancet. 388(10043):505-17. doi: 10.1016/S0140-6736(15)01124-1.
Haass C., Kaether C., Thinakaran G. and Sisodia S. 2012 Trafficking and Proteolytic Processing of APP. Cold Spring. Harb. Perspect. Med. 2012(2): a006270. DOI: 10.1101/cshperspect.a006270.
Walker LC. 2020 Aβ plaques. Free Neuropathol. 1: 31. https://doi.org/10.17879/freeneuropathology-2020-3025.
De Strooper B. 2010 Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process. Physiol. Rev. 90: 465–494. https://doi.org/10.1152/physrev.00023.2009.
Hardy JA. and Higgins GA. 1992 Alzheimer’s disease: the amyloid cascade hypothesis. Science. 256(5054): 184–185. DOI: 10.1126/science.1566067.
Tanzi RE. 2005 The synaptic Aβ hypothesis of Alzheimer disease. Nat. Neurosci. 8: 977–979. https://doi.org/10.1038/nn0805-977.
Thinakaran G., Teplow DB., Siman R., Greenberg B. and Sisodia SS. 1996 Metabolism of the ‘‘Swedish’’ amyloid precursor protein variant in neuro2a (N2a) cells. Evidence that cleavage at the ‘‘beta-secretase’’ site occurs in the golgi apparatus. J. Biol. Chem. 271(16): 9390–9397. https://doi.org/10.1074/jbc.271.16.9390.
Catalano SM., Dodson EC., Henze DA., Joyce JG., Krafft GA. and Kinney GG. 2006 The role of amyloid-beta derived diffusible ligands (ADDLs) in Alzheimer's disease. Curr. Top Med. Chem. 6(6):597-608. doi:10.2174/156802606776743066.
Kuo YM., Emmerling MR., Vigo-Pelfrey C., Kasunic TC., Kirkpatrick JB., Murdoch GH., Ball MJ. and Roher AE. 1996 Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J. Biol. Chem. 271(8):4077-81. doi: 10.1074/jbc.271.8.4077.
Haass C. and Selkoe DJ. 2007 Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 8(2): 101-112. DOI: 10.1038/nrm2101.
Tomiyama T. and Shimada H. 2020 APP Osaka Mutation in Familial Alzheimer’s Disease-Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance. Int. J. Mol. Sci. 21(4): 1413. doi: 10.3390/ijms21041413.
Walsh DM. and Selkoe DJ. 2020 Amyloid beta-protein and beyond: the path forward in Alzheimer’s disease. Curr. Opin. Neurobiol. 61: 116-124. doi: 10.1016/j.conb.2020.02.003.
Delabio R., Rasmussen L., Mizumoto I., Viani GA., Chen EA., Villares J. and Payao SL. 2014 PSEN1 and PSEN2 gene expression in Alzheimer's disease brain: a new approach. J. Alzheimer's Dise. 42(3): 757-760. doi: 10.3233/JAD-140033.
Hardy J. and Selkoe DJ. 2002 The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 297(5580): 353-356. doi: 10.1126/science.1072994.
Welander H., Frånberg J., Graff C., Sundström E. Winblad B. and Tjernberg LO. 2009 Aβ43 is more frequent than Aβ40 in amyloid plaque cores from Alzheimer disease brains. J. neurochem. 110(2): 697-706. DOI: 10.1111/j.1471-4159.2009.06170.x.
De Strooper B., Vassar R. and Golde T. 2010 The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat. revie. neurol. 6(2): 99-107. doi: 10.1038/nrneurol.2009.218.
Hong L., Koelsch G., Lin X., Wu S., Terzyan S., Ghosh AK. and Tang J. 2000 Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor. Science. 290(5489): 150-153. doi: 10.1126/science.290.5489.150.
Singer O., Ikawa M., Hoong N., Campbell G. and Verma IM. 2004 Gene Knockdown in Mice by Using Lentiviral Vectors Expressing Small Interfering RNA. Molecul. Therapy. 9(4): S380. DOI:10.1016/j.ymthe.2004.06.932.
Singer O., Marr RA., Rockenstein E., Crews L., Coufal NG. and Gage FH. and Masliah E. 2005 Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat. neurosci. 8(10): 1343-1349. doi: 10.1038/nn1531.
Stewart SA., Dykxhoorn DM., Palliser D., Mizuno H., Yu EY., An DS., Sabatini DM., Chen ISY., Hahn WC., Sharp PA., Weinberg RA. and Novina CD. 2003 Lentivirus-delivered stable gene silencing by RNAi in primary cells. Rna. 9(4): 493-501. DOI: 10.1261/rna.2192803.
Peng KA. and Masliah E. 2010 Lentivirus-expressed siRNA vectors against Alzheimer disease. Lentivirus Gene Engineering Protocols: Second Edition. 614:215-224. doi: 10.1007/978-1-60761-533-0_15.
Sun SC. 2011 Non-canonical NF-κB signaling pathway. Cell res. 21(1): 71-85. doi: 10.1038/cr.2010.177.
Jha NK., Chen WC., Kumar S., Dubey R., Tsai LW., Kar R., Jha SK., Gupta PK., Sharma A., Gundamaraju R., Pant K., Mani S., Singh SK., Maccioni RB., Datta T., Singh SK., Gupta G., Prasher P., Dua K., Dey A., Sharma C. and Mughal YH., Ruokolainen J., Kesari KK. and Ojha S. 2022 Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review. Open Biol. 12(3): 210289, 1-38. doi: 10.1098/rsob.210289.
Chen CH., Zhou W., Liu S., Deng Y., Cai F., Tone M. and Song W. 2012 Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer's disease. Int. J. Neuropsychopharmacol. 15(1): 77-90. doi: 10.1017/S1461145711000149.
Wang F., Zou Z., Gong Y., Yuan D., Chen X. and Sun T. 2017 Regulation of human brain microvascular endothelial cell adhesion and barrier functions by memantine. J. Molecul. Neurosci. 62(1): 123-129. doi: 10.1007/s12031-017-0917-x.
Medeiros R., Kitazawa M., Passos GF., Baglietto-Vargas D., Cheng D., Cribbs DH. and LaFerla FM. 2013 Aspirin-triggered lipoxin A4 stimulates alternative activation of microglia and reduces Alzheimer disease–like pathology in mice. The American j. pathol. 182(5): 1780-1789. DOI: 10.1016/j.ajpath.2013.01.051.
Cai Z., Zhao Y., Yao S., and Zhao B. 2011 Increases in β-amyloid protein in the hippocampus caused by diabetic metabolic disorder are blocked by minocycline through inhibition of NF-κB pathway activation. Pharmacol. Reports. 63(2): 381-391. doi: 10.1016/s1734-1140(11)70504-7.
Kong FG., Jiang X., Wang R., Zhai S., Zhang Y., and Wang D. 2020 Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease. J. Neuroinflamm. 17(1)305:.1-15. doi: 10.1186/s12974-020-01967-2.
De Strooper B., Iwatsubo T. and Wolfe MS. 2012 Presenilins and γ-secretase: structure, function, and role in Alzheimer disease. Cold Spring. Harbor perspect. Medi. 2(1): a006304. doi: 10.1101/cshperspect.a006304.
Sogorb-Esteve A., García-Ayllón MS., Llansola M., Felipo V., Blennow K., and Sáez-Valero J. 2018 Inhibition of γ-secretase leads to an increase in presenilin-1. Molecul. Neurobiol. 55(6): 5047-5058. doi: 10.1007/s12035-017-0705-1.
Takasugi N., Tomita T., Hayashi I., Tsuruoka M., Niimura M., Takahashi Y. and Iwatsubo T. 2003 The role of presenilin cofactors in the γ-secretase complex. Nature. 422(6930): 438-441. doi: 10.1038/nature01506.
Fraering PC., Ye W., LaVoie MJ., Ostaszewski BL., Selkoe DJ. And Wolfe MS. 2005 γ-Secretase substrate selectivity can be modulated directly via interaction with a nucleotide-binding site. J. Biol. Chem. 280(51): 41987-41996. doi: 10.1074/jbc.M501368200.
Netzer WJ., Dou F., Cai D., Veach D., Jean S., Li Y. and Greengard P. 2003 Gleevec inhibits β-amyloid production but not Notch cleavage. Proceed. Nation. Aca. Sci. 100(21): 12444-12449. doi: 10.1073/pnas.1534745100.
De Strooper B., Annaert W., Cupers P., Saftig P., Craessaerts K., Mumm JS., Schroeter EH., Schrijvers V., Wolfe MS., Ray WJ., Goate A. and Kopan R. 1999 A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 398 (6727): 518–22. doi:10.1038/19083.
Marambaud P., Wen PH., Dutt A., Shioi J., Takashima A., Siman R. and Robakis NK. 2003 A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell. 114 (5): 635–45. doi:10.1016/j.cell.2003.08.008.
Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V., Baki L., Wen P., Efthimiopoulos S., Shao Z., Wisniewski T. and Robakis NK. 2002 A presenilin- 1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 21 (8): 1948–56. doi:10.1093/emboj/21.8.1948.
Georgakopoulos A., Litterst C., Ghersi E., Baki L., Xu C., Serban G. and Robakis NK. 2006 Metalloproteinase/Presenilin1 processing of ephrinB regulates EphB-induced Src phosphorylation and signaling. EMBO J. 25 (6): 1242–52. doi:10.1038/sj.emboj.7601031.
Ni CY., Murphy MP., Golde TE. and Carpenter G. 2001 gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science. 294 (5549): 2179–81. doi:10.1126/science.1065412.
Lammich S., Okochi M., Takeda M., Kaether C., Capell A., Zimmer AK., Edbauer D., Walter J., Steiner H., Haass C. 2002 Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide. J. Biol. Chem. 277 (47): 44754–9. doi:10.1074/jbc.M206872200.
Louvi A. and Artavanis-Tsakonas S. 2006 Notch signalling in vertebrate neural development. Nat. Rev. Neurosci. 7(2): 93-102. doi: 10.1038/nrn1847.
Ables JL., Breunig JJ., Eisch AJ. and Rakic P. 2011 Not (ch) just development: Notch signalling in the adult brain. Nat. Rev. Neurosci. 12(5): 269-283. doi: 10.1038/nrn3024.
Kumar D., Ganeshpurkar A., Kumar D., Modi G., Gupta SK. and Singh SK. 2018 Secretase inhibitors for the treatment of Alzheimer's disease: Long road ahead. Europ. J. Medi. Chem. 148: 436-452. doi:10.1016/j.ejmech.2018.02.035.
Adrienne T Black. 2016 Chapter 13 - Dermatological Drugs, Topical Agents, and Cosmetics (Journal/book)Side Effects of Drugs Annual. Editor(s): Sidhartha D. Ray, Side Effects of Drugs Annual, Elsevier. 38: 129-141. https://doi.org/10.1016/bs.seda.2016.08.002.
Bateman RJ., Xiong C., Benzinger TL., Fagan AM., Goate A., Fox NC., Marcus DS., Cairns NJ., Xie X., Blazey TM., Holtzman DM., Santacruz A., Buckles V., Oliver A., Moulder K., Aisen PS., Ghetti B., Klunk WE., McDade E., Martins RN., Masters CL., Mayeux R., Ringman JM., Rossor MN., Schofield PR., Sperling RA., Salloway S. and Morris JC. 2012 Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N. Engl. J. Med. 367(9):795-804. doi: 10.1056/NEJMoa1202753.
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