Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

The Structure and Function of α, β and γ-Secretase as Therapeutic Target Enzymes in the Development of Alzheimer’s Disease: A Review

Author(s): Syed S. Ahmad*, Shahzad Khan, Mohammad A. Kamal and Umam Wasi

Volume 18, Issue 9, 2019

Page: [657 - 667] Pages: 11

DOI: 10.2174/1871527318666191011145941

Price: $65

Abstract

Alzheimer's disease is a progressive neurodegenerative disorder that affects the central nervous system. There are several factors that cause AD, like, intracellular hyperphosphorylated Tau tangles, collection of extracellular Amyloid-β42 and generation of reactive oxygen species due to mitochondrial dysfunction. This review analyses the most active target of AD and both types of AD-like early-onset AD and late-onset AD. BACE1 is a β-secretase involved in the cleavage of amyloid precursor protein and the pathogenesis of Alzheimer's disease. The presenilin proteins play a critical role in the pathogenesis of Alzheimer malady by intervening the intramembranous cleavage of amyloid precursor protein and the generation of amyloid β. The two homologous proteins PS1 and PS2 speak to the reactant subunits of particular γ-secretase edifices that intercede an assortment of cellular processes. Natural products are common molecular platforms in drug development in AD. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target in AD. Presently, there are a few theories clarifying the early mechanisms of AD pathogenesis. Recently, research advancements in the field of nanotechnology, which utilize macromolecular strategies to make drugs in nanoscale measurements, offer nanotechnology-based diagnostic tools and drug carriers which are highly sensitive for effective drug targeting in the treatment of Alzheimer’s disease.

Keywords: Alzheimer's disease, secretase activity, nanotechnology, BBB, APP, treatment.

Graphical Abstract

[1]
Femminella GD, Thayanandan T, Calsolaro V, et al. Imaging and molecular mechanisms of Alzheimer’s disease: A review. Int J Mol Sci 2018; 19(12): 3702.
[http://dx.doi.org/10.3390/ijms19123702] [PMID: 30469491]
[2]
Prince M, Wimo A, Guerchet M, Ali G, Wu Y, Prina M. World Alzheimer Report-The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends; Alzheimer’s Disease International. London, UK: ADI 2015. [cited: 15 October 2004]; Available from:. https://www.alz.co.uk/research/WorldAlzheimer Report2015.pdf
[3]
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement 2018; 14: 367-429.
[http://dx.doi.org/10.1016/j.jalz.2018.02.001]
[4]
Ahmad SS, Akhtar S. Danish Rizvi SM, et al.. Screening and elucidation of selected natural compounds for anti- Alzheimer’s potential targeting BACE-1 enzyme: A case computational study. Curr Comput Aided Drug Des 2017; 13(4): 311-8.
[http://dx.doi.org/10.2174/1573409913666170414123825] [PMID: 28413992]
[5]
Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev 2011; 35(6): 1397-409.
[http://dx.doi.org/10.1016/j.neubiorev.2011.03.001] [PMID: 21392524]
[6]
Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer’s disease: An appraisal for the development of therapeutics. Nat Rev Drug Discov 2011; 10(9): 698-712.
[http://dx.doi.org/10.1038/nrd3505] [PMID: 21852788]
[7]
Maccioni RB, Farías G, Morales I, Navarrete L. The revitalized tau hypothesis on Alzheimer’s disease. Arch Med Res 2010; 41(3): 226-31.
[http://dx.doi.org/10.1016/j.arcmed.2010.03.007] [PMID: 20682182]
[8]
Markesbery WR. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 1997; 23(1): 134-47.
[http://dx.doi.org/10.1016/S0891-5849(96)00629-6] [PMID: 9165306]
[9]
Craddock TJ, Tuszynski JA, Chopra D, et al. The zinc dyshomeostasis hypothesis of Alzheimer’s disease. PLoS One 2012; 7(3)e33552
[http://dx.doi.org/10.1371/journal.pone.0033552] [PMID: 22457776]
[10]
Yamashima T. Reconsider Alzheimer’s disease by the ‘calpain-cathepsin hypothesis’--a perspective review. Prog Neurobiol 2013; 105: 1-23.
[http://dx.doi.org/10.1016/j.pneurobio.2013.02.004] [PMID: 23499711]
[11]
Ahmad SS, Akhtar S, Jamal QM, et al. Multiple targets for the management of Alzheimer’s disease. CNS Neurol Disord Drug Targets 2016; 15(10): 1279-89.
[http://dx.doi.org/10.2174/1871527315666161003165855] [PMID: 27712576]
[12]
Selnes OA, Vinters HV. Vascular cognitive impairment. Nat Clin Pract Neurol 2006; 2(10): 538-47.
[http://dx.doi.org/10.1038/ncpneuro0294] [PMID: 16990827]
[13]
Nelson PT, Jicha GA, Schmitt FA, et al. Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: Neuritic plaques and neurofibrillary tangles “do count” when staging disease severity. J Neuropathol Exp Neurol 2007; 66(12): 1136-46.
[http://dx.doi.org/10.1097/nen.0b013e31815c5efb] [PMID: 18090922]
[14]
Vassar R, Kovacs DM, Yan R, Wong PC. The β-secretase enzyme BACE in health and Alzheimer’s disease: Regulation, cell biology, function, and therapeutic potential. J Neurosci 2009; 29(41): 12787-94.
[http://dx.doi.org/10.1523/JNEUROSCI.3657-09.2009] [PMID: 19828790]
[15]
Akter K, Lanza EA, Martin SA, Myronyuk N, Rua M, Raffa RB. Diabetes mellitus and Alzheimer’s disease: Shared pathology and treatment? Br J Clin Pharmacol 2011; 71(3): 365-76.
[http://dx.doi.org/10.1111/j.1365-2125.2010.03830.x] [PMID: 21284695]
[16]
Götz J, Ittner LM. Animal models of Alzheimer’s disease and frontotemporal dementia. Nat Rev Neurosci 2008; 9(7): 532-44.
[http://dx.doi.org/10.1038/nrn2420] [PMID: 18568014]
[17]
Winblad B, Jelic V. Long-term treatment of Alzheimer disease: Efficacy and safety of acetylcholinesterase inhibitors. Alzheimer Dis Assoc Disord 2004; 18(Suppl. 1): S2-8.
[http://dx.doi.org/10.1097/01.wad.0000127495.10774.a4] [PMID: 15249842]
[18]
Götz J, Ittner LM, Lim YA. Common features between diabetes mellitus and Alzheimer’s disease. Cell Mol Life Sci 2009; 66(8): 1321-5.
[http://dx.doi.org/10.1007/s00018-009-9070-1] [PMID: 19266159]
[19]
Hauser WA, Morris ML, Heston LL, Anderson VE. Seizures and myoclonus in patients with Alzheimer’s disease. Neurology 1986; 36(9): 1226-30.
[http://dx.doi.org/10.1212/WNL.36.9.1226] [PMID: 3092131]
[20]
Naj AC, Schellenberg GD. Alzheimer’s Disease Genetics Consortium (ADGC). Genomic variants, genes, and pathways of Alzheimer’s disease: An overview. Am J Med Genet B Neuropsychiatr Genet 2017; 174(1): 5-26.
[http://dx.doi.org/10.1002/ajmg.b.32499] [PMID: 27943641]
[21]
Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991; 349(6311): 704-6.
[http://dx.doi.org/10.1038/349704a0] [PMID: 1671712]
[22]
Levy-Lahad E, Wasco W, Poorkaj P, et al. Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 1995; 269(5226): 973-7.
[http://dx.doi.org/10.1126/science.7638622] [PMID: 7638622]
[23]
Rogaev EI, Sherrington R, Rogaeva EA, et al. Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 1995; 376(6543): 775-8.
[http://dx.doi.org/10.1038/376775a0] [PMID: 7651536]
[24]
Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 1995; 375(6534): 754-60.
[http://dx.doi.org/10.1038/375754a0] [PMID: 7596406]
[25]
Strittmatter WJ, Weisgraber KH, Huang DY, et al. Binding of human apolipoprotein E to synthetic amyloid beta peptide: Isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA 1993; 90(17): 8098-102.
[http://dx.doi.org/10.1073/pnas.90.17.8098] [PMID: 8367470]
[26]
Förstl H, Kurz A. Clinical features of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 1999; 249(6): 288-90.
[http://dx.doi.org/10.1007/s004060050101] [PMID: 10653284]
[27]
Bature F, Guinn BA, Pang D, Pappas Y. Signs and symptoms preceding the diagnosis of Alzheimer’s disease: A systematic scoping review of literature from 1937 to 2016. BMJ Open 2017; 7(8) e015746
[http://dx.doi.org/10.1136/bmjopen-2016-015746] [PMID: 28851777]
[28]
Braskie MN, Jahanshad N, Stein JL, et al. Common Alzheimer’s disease risk variant within the CLU gene affects white matter microstructure in young adults. J Neurosci 2011; 31(18): 6764-70.
[http://dx.doi.org/10.1523/JNEUROSCI.5794-10.2011] [PMID: 21543606]
[29]
Shinohara M, Fujioka S, Murray ME, et al. Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer’s disease. Brain 2014; 137(Pt 5): 1533-49.
[http://dx.doi.org/10.1093/brain/awu046] [PMID: 24625695]
[30]
Cole SL, Vassar R. The basic biology of BACE1: A key therapeutic target for Alzheimer’s disease. Curr Genomics 2007; 8(8): 509-30.
[http://dx.doi.org/10.2174/138920207783769512] [PMID: 19415126]
[31]
Seubert P, Oltersdorf T, Lee MG, et al. Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide. Nature 1993; 361(6409): 260-3.
[http://dx.doi.org/10.1038/361260a0] [PMID: 7678698]
[32]
Haass C, Schlossmacher MG, Hung AY, et al. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 1992; 359(6393): 322-5.
[http://dx.doi.org/10.1038/359322a0] [PMID: 1383826]
[33]
Vassar R, Bennett BD, Babu-Khan S, et al. Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999; 286(5440): 735-41.
[http://dx.doi.org/10.1126/science.286.5440.735] [PMID: 10531052]
[34]
Marcinkiewicz M, Seidah NG. Coordinated expression of β-amyloid precursor protein and the putative β-secretase BACE and α-secretase ADAM10 in mouse and human brain. J Neurochem 2000; 75(5): 2133-43.
[http://dx.doi.org/10.1046/j.1471-4159.2000.0752133.x] [PMID: 11032903]
[35]
Vassar R, Kovacs DM, Yan R, Wong PC. The β-secretase enzyme BACE in health and Alzheimer’s disease: Regulation, cell biology, function, and therapeutic potential. J Neurosci 2009; 29(41): 12787-94.
[http://dx.doi.org/10.1523/JNEUROSCI.3657-09.2009] [PMID: 19828790]
[36]
Selkoe DJ, 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]
[37]
Femminella GD, Thayanandan T, Calsolaro V, et al. Imaging and molecular mechanisms of Alzheimer’s Disease: A review. Int J Mol Sci 2018; 19(12): 3702.
[http://dx.doi.org/10.3390/ijms19123702] [PMID: 30469491]
[38]
Scheltens P, Blennow K, Breteler MM, et al. Alzheimer’s disease. Lancet 2016; 388(10043): 505-17.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[39]
Haass C, Kaether C, Thinakaran G, Sisodia S. Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med 2012; 2(5) a006270.
[http://dx.doi.org/10.1101/cshperspect.a006270] [PMID: 22553493]
[40]
Wilkins HM, Swerdlow RH. Amyloid precursor protein processing and bioenergetics. Brain Res Bull 2017; 133: 71-9.
[http://dx.doi.org/10.1016/j.brainresbull.2016.08.009] [PMID: 27545490]
[41]
Lai A, Sisodia SS, Trowbridge IS. Characterization of sorting signals in the beta-amyloid precursor protein cytoplasmic domain. J Biol Chem 1995; 270(8): 3565-73.
[http://dx.doi.org/10.1074/jbc.270.8.3565] [PMID: 7876092]
[42]
La Rosa LR, Perrone L, Nielsen MS, Calissano P, Andersen OM, Matrone C. Y682G mutation of amyloid precursor protein promotes endo-lysosomal dysfunction by disrupting APP-SorLA interaction. Front Cell Neurosci 2015; 9: 109.
[http://dx.doi.org/10.3389/fncel.2015.00109] [PMID: 25904844]
[43]
Perez RG, Soriano S, Hayes JD, et al. Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42. J Biol Chem 1999; 274(27): 18851-6.
[http://dx.doi.org/10.1074/jbc.274.27.18851] [PMID: 10383380]
[44]
Zhang YW, Thompson R, Zhang H, Xu H. APP processing in Alzheimer’s disease. Mol Brain 2011; 4: 3.
[http://dx.doi.org/10.1186/1756-6606-4-3] [PMID: 21214928]
[45]
Chen GF, Xu TH, Yan Y, et al. Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 2017; 38(9): 1205-35.
[http://dx.doi.org/10.1038/aps.2017.28] [PMID: 28713158]
[46]
Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ. Beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 1993; 268(5): 3021-4.
[PMID: 8428976]
[47]
Lammich S, Kojro E, Postina R, et al. Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 1999; 96(7): 3922-7.
[http://dx.doi.org/10.1073/pnas.96.7.3922] [PMID: 10097139]
[48]
Furukawa K, Sopher BL, Rydel RE, et al. Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem 1996; 67(5): 1882-96.
[http://dx.doi.org/10.1046/j.1471-4159.1996.67051882.x] [PMID: 8863493]
[49]
Skovronsky DM, Moore DB, Milla ME, Doms RW, Lee VM. Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-Golgi network. J Biol Chem 2000; 275(4): 2568-75.
[http://dx.doi.org/10.1074/jbc.275.4.2568] [PMID: 10644715]
[50]
De Strooper B, Vassar R, Golde T. The secretases: Enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol 2010; 6(2): 99-107.
[http://dx.doi.org/10.1038/nrneurol.2009.218] [PMID: 20139999]
[51]
Bandyopadhyay S, Goldstein LE, Lahiri DK, Rogers JT. Role of the APP non-amyloidogenic signaling pathway and targeting alpha-secretase as an alternative drug target for treatment of Alzheimer’s disease. Curr Med Chem 2007; 14(27): 2848-64.
[http://dx.doi.org/10.2174/092986707782360060] [PMID: 18045131]
[52]
Hong-Qi Y, Zhi-Kun S, Sheng-Di C. Current advances in the treatment of Alzheimer’s disease: Focused on considerations targeting Aβ and tau. Transl Neurodegener 2012; 1(1): 21.
[http://dx.doi.org/10.1186/2047-9158-1-21] [PMID: 23210837]
[53]
De Strooper B, Annaert W. Proteolytic processing and cell biological functions of the amyloid precursor protein. J Cell Sci 2000; 113(Pt 11): 1857-70.
[PMID: 10806097]
[54]
MacLeod R, Hillert EK, Cameron RT, Baillie GS. The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer’s disease. Future Sci OA 2015; 1(3): FSO11.
[http://dx.doi.org/10.4155/fso.15.9] [PMID: 28031886]
[55]
Thinakaran G, Borchelt DR, Lee MK, et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 1996; 17(1): 181-90.
[http://dx.doi.org/10.1016/S0896-6273(00)80291-3] [PMID: 8755489]
[56]
Steiner H, Kostka M, Romig H, et al. Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases. Nat Cell Biol 2000; 2(11): 848-51.
[http://dx.doi.org/10.1038/35041097] [PMID: 11056541]
[57]
Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, Selkoe DJ. Complex N-linked glycosylated nicastrin associates with active gamma-secretase and undergoes tight cellular regulation. J Biol Chem 2002; 277(38): 35113-7.
[http://dx.doi.org/10.1074/jbc.M204446200] [PMID: 12130643]
[58]
Goutte C, Tsunozaki M, Hale VA, Priess JR. APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos. Proc Natl Acad Sci USA 2002; 99(2): 775-9.
[http://dx.doi.org/10.1073/pnas.022523499] [PMID: 11792846]
[59]
Francis R, McGrath G, Zhang J, et al. APH-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 2002; 3(1): 85-97.
[http://dx.doi.org/10.1016/S1534-5807(02)00189-2] [PMID: 12110170]
[60]
Hébert SS, Serneels L, Dejaegere T, et al. Coordinated and widespread expression of γ-secretase in vivo: Evidence for size and molecular heterogeneity. Neurobiol Dis 2004; 17(2): 260-72.
[http://dx.doi.org/10.1016/j.nbd.2004.08.002] [PMID: 15474363]
[61]
Saito S, Araki W. Expression profiles of two human APH-1 genes and their roles in formation of presenilin complexes. Biochem Biophys Res Commun 2005; 327(1): 18-22.
[http://dx.doi.org/10.1016/j.bbrc.2004.11.130] [PMID: 15629423]
[62]
Esler WP, Kimberly WT, Ostaszewski BL, et al. Activity-dependent isolation of the presenilin-gamma-secretase complex reveals nicastrin and a gamma substrate. Proc Natl Acad Sci USA 2002; 99(5): 2720-5.
[http://dx.doi.org/10.1073/pnas.052436599] [PMID: 11867728]
[63]
Borchelt DR, Thinakaran G, Eckman CB, et al. Familial Alzheimer’s disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 1996; 17(5): 1005-13.
[http://dx.doi.org/10.1016/S0896-6273(00)80230-5] [PMID: 8938131]
[64]
Ertekin-Taner N. Genetics of Alzheimer’s disease: A centennial review. Neurol Clin 2007; 25(3): 611-67.
[http://dx.doi.org/10.1016/j.ncl.2007.03.009] [PMID: 17659183]
[65]
Radde R, Bolmont T, Kaeser SA, et al. Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep 2006; 7(9): 940-6.
[http://dx.doi.org/10.1038/sj.embor.7400784] [PMID: 16906128]
[66]
Doody RS, Farlow M, Aisen PS. Alzheimer’s disease cooperative study data analysis and publication committee. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer’s disease. N Engl J Med 2014; 370(15): 1460.
[PMID: 24716687]
[67]
Salloway S, Sperling R, Fox NC, et al. Bapineuzumab 301 and 302 Clinical Trial Investigators. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 2014; 370(4): 322-33.
[http://dx.doi.org/10.1056/NEJMoa1304839] [PMID: 24450891]
[68]
Sharma P, Tripathi A, Tripathi PN, et al. Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer’s disease. Eur J Med Chem 2019; 167: 510-24.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.030] [PMID: 30784883]
[69]
Schaduangrat N, Prachayasittikul V, Choomwattana S, et al. Multidisciplinary approaches for targeting the secretase protein family as a therapeutic route for Alzheimer’s disease. Med Res Rev 2019; 39(5): 1730-78.
[http://dx.doi.org/10.1002/med.21563] [PMID: 30628099]
[70]
Prachayasittikul V, Worachartcheewan A, Shoombuatong W, et al. Computer-aided drug design of bioactive natural products. Curr Top Med Chem 2015; 15(18): 1780-800.
[http://dx.doi.org/10.2174/1568026615666150506151101] [PMID: 25961523]
[71]
Jiang XW, Lu HY, Xu Z, et al. In silico analyses for key genes and molecular genetic mechanism in epilepsy and Alzheimer’s disease. CNS Neurol Disord Drug Targets 2018; 17(8): 608-17.
[http://dx.doi.org/10.2174/1871527317666180724150839] [PMID: 30047339]
[72]
Singh A, Hasan A, Tiwari S, Pandey LM. Therapeutic advancement in Alzheimer disease: New hopes on the horizon? CNS Neurol Disord Drug Targets 2018; 17(8): 571-89.
[http://dx.doi.org/10.2174/1871527317666180627122448] [PMID: 29952273]
[73]
Iman K, Mirza MU, Mazhar N, Vanmeert M, Irshad I, Kamal MA. In silico structure-based identification of novel acetylcholinesterase inhibitors against Alzheimer’s disease. CNS Neurol Disord Drug Targets 2018; 17(1): 54-68.
[http://dx.doi.org/10.2174/1871527317666180115162422] [PMID: 29336270]
[74]
Jeon SY, Kwon SH, Seong YH, et al. β-secretase (BACE1)-inhibiting stilbenoids from Smilax rhizoma. Phytomedicine 2007; 14(6): 403-8.
[http://dx.doi.org/10.1016/j.phymed.2006.09.003] [PMID: 17084604]
[75]
Jeon SY, Bae K, Seong YH, Song KS. Green tea catechins as a BACE1 (beta-secretase) inhibitor. Bioorg Med Chem Lett 2003; 13(22): 3905-8.
[http://dx.doi.org/10.1016/j.bmcl.2003.09.018] [PMID: 14592472]
[76]
Marumoto S, Miyazawa M. Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor. Bioorg Med Chem 2012; 20(2): 784-8.
[http://dx.doi.org/10.1016/j.bmc.2011.12.002] [PMID: 22222157]
[77]
Jung HA, Jin SE, Choi RJ, et al. Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1. Life Sci 2010; 87(13-14): 420-30.
[http://dx.doi.org/10.1016/j.lfs.2010.08.005] [PMID: 20736023]
[78]
Park IH, Jeon SY, Lee HJ, Kim SI, Song KS. A β-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus. Planta Med 2004; 70(2): 143-6.
[http://dx.doi.org/10.1055/s-2004-815491] [PMID: 14994192]
[79]
Youn K, Yu Y, Lee J, Jeong WS, Ho CT, Jun M. Polymethoxyflavones: Novel β-secretase (BACE1) inhibitors from citrus peels. Nutrients 2017; 9(9): 973.
[http://dx.doi.org/10.3390/nu9090973] [PMID: 28869548]
[80]
Youn K, Park JH, Lee S, et al. BACE1 inhibition by Genistein: Biological evaluation, kinetic analysis, and molecular docking simulation. J Med Food 2018; 21(4): 416-20.
[http://dx.doi.org/10.1089/jmf.2017.4068] [PMID: 29444415]
[81]
Kumar S, Chowdhury S, Kumar S. In silico repurposing of antipsychotic drugs for Alzheimer’s disease. BMC Neurosci 2017; 18(1): 76.
[http://dx.doi.org/10.1186/s12868-017-0394-8] [PMID: 29078760]
[82]
Hung SY, Fu WM. Drug candidates in clinical trials for Alzheimer’s disease. J Biomed Sci 2017; 24(1): 47.
[http://dx.doi.org/10.1186/s12929-017-0355-7] [PMID: 28720101]
[83]
Wang K, Sun W, Zhang L, et al. Oleanolic acid ameliorates Aβ25-35 injection-induced memory deficit in Alzheimer’s disease model rats by maintaining synaptic plasticity. CNS Neurol Disord Drug Targets 2018; 17(5): 389-99.
[http://dx.doi.org/10.2174/1871527317666180525113109] [PMID: 29793416]
[84]
Beg T, Jyoti S, Naz F, et al. Protective effect of Kaempferol on the transgenic drosophila model of Alzheimer’s disease. CNS Neurol Disord Drug Targets 2018; 17(6): 421-9.
[http://dx.doi.org/10.2174/1871527317666180508123050] [PMID: 29745345]
[85]
Bais S, Kumari R, Prashar Y. Ameliorative effect of trans-sinapic acid and its protective role in cerebral hypoxia in aluminium chloride induced dementia of Alzheimer’s type. CNS Neurol Disord Drug Targets 2018; 17(2): 144-54.
[http://dx.doi.org/10.2174/1871527317666180309130912] [PMID: 29521253]
[86]
Xinyu D, Yuntao L, Yuejiao Z. Recent developments of nanotechnology for Alzheimer’s disease diagnosis and therapy. Glob J Nano 2018; 4(4): 555644
[87]
Leszek J, Md Ashraf G, Tse WH, et al. Nanotechnology for Alzheimer disease. Curr Alzheimer Res 2017; 14(11): 1182-9.
[http://dx.doi.org/10.2174/1567205014666170203125008] [PMID: 28164767]
[88]
Nazıroğlu M, Muhamad S, Pecze L. Nanoparticles as potential clinical therapeutic agents in Alzheimer’s disease: Focus on selenium nanoparticles. Expert Rev Clin Pharmacol 2017; 10(7): 773-82.
[http://dx.doi.org/10.1080/17512433.2017.1324781] [PMID: 28463572]
[89]
Gregori M, Masserini M, Mancini S. Nanomedicine for the treatment of Alzheimer’s disease. Nanomedicine (Lond) 2015; 10(7): 1203-18.
[http://dx.doi.org/10.2217/nnm.14.206] [PMID: 25929574]
[90]
Mullane K, Williams M. Alzheimer’s therapeutics: Continued clinical failures question the validity of the amyloid hypothesis-but what lies beyond? Biochem Pharmacol 2013; 85(3): 289-305.
[http://dx.doi.org/10.1016/j.bcp.2012.11.014] [PMID: 23178653]
[91]
Lauzon MA, Daviau A, Marcos B, Faucheux N. Nanoparticle-mediated growth factor delivery systems: A new way to treat Alzheimer’s disease. J Control Release 2015; 206: 187-205.
[http://dx.doi.org/10.1016/j.jconrel.2015.03.024] [PMID: 25804873]
[92]
Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: An overview: Structure, regulation, and clinical implications. Neurobiol Dis 2004; 16(1): 1-13.
[http://dx.doi.org/10.1016/j.nbd.2003.12.016] [PMID: 15207256]
[93]
Lockman PR, Oyewumi MO, Koziara JM, Roder KE, Mumper RJ, Allen DD. Brain uptake of thiamine-coated nanoparticles. J Control Release 2003; 93(3): 271-82.
[http://dx.doi.org/10.1016/j.jconrel.2003.08.006] [PMID: 14644577]
[94]
Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, et al. Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem Biophys Res Commun 2010; 393(4): 649-55.
[http://dx.doi.org/10.1016/j.bbrc.2010.02.046] [PMID: 20153731]
[95]
Wilson B. Brain targeting PBCA nanoparticles and the blood-brain barrier. Nanomedicine (Lond) 2009; 4(5): 499-502.
[http://dx.doi.org/10.2217/nnm.09.29] [PMID: 19572813]
[96]
Cacciatore I, Ciulla M, Fornasari E, Marinelli L, Di Stefano A. Solid lipid nanoparticles as a drug delivery system for the treatment of neurodegenerative diseases. Expert Opin Drug Deliv 2016; 13(8): 1121-31.
[http://dx.doi.org/10.1080/17425247.2016.1178237] [PMID: 27073977]
[97]
Elnaggar YSR, Etman SM, Abdelmonsif DA, Abdallah OY. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer’s disease: Optimization, biological efficacy, and potential toxicity. J Pharm Sci 2015; 104: 3544-56.
[http://dx.doi.org/10.1002/jps.24557]
[98]
Sinha J, Das N, Basu MK. Liposomal antioxidants in combating ischemia-reperfusion injury in rat brain. Biomed Pharmacother 2001; 55(5): 264-71.
[http://dx.doi.org/10.1016/S0753-3322(01)00060-9] [PMID: 11428552]
[99]
Kim D, Kwon HJ, Hyeon T. Magnetite/ceria nanoparticle assemblies for extracorporeal cleansing of amyloid-β in Alzheimer’s disease. Adv Mater 2019; 31(19): e1807965
[http://dx.doi.org/10.1002/adma.201807965] [PMID: 30920695]
[100]
Wong LR, Ho PC. Role of serum albumin as a nanoparticulate carrier for nose-to-brain delivery of R-flurbiprofen: Implications for the treatment of Alzheimer’s disease. J Pharm Pharmacol 2018; 70(1): 59-69.
[http://dx.doi.org/10.1111/jphp.12836] [PMID: 29034965]
[101]
Hajipour MJ, Santoso MR, Rezaee F, Aghaverdi H, Mahmoudi M, Perry G. Advances in Alzheimer’s diagnosis and therapy: The implications of nanotechnology. Trends Biotechnol 2017; 35(10): 937-53.
[http://dx.doi.org/10.1016/j.tibtech.2017.06.002] [PMID: 28666544]
[102]
Gwinn MR, Vallyathan V. Nanoparticles: Health effects--pros and cons. Environ Health Perspect 2006; 114(12): 1818-25.
[http://dx.doi.org/10.1289/ehp.8871] [PMID: 17185269]
[103]
Kaushik A, Jayant RD, Tiwari S, Vashist A, Nair M. Nano-biosensors to detect beta-amyloid for Alzheimer’s disease management. Biosens Bioelectron 2016; 80: 273-87.
[http://dx.doi.org/10.1016/j.bios.2016.01.065] [PMID: 26851586]
[104]
Verma A, Kumar A, Debnath M. Molecular docking and simulation studies to give insight of surfactin amyloid interaction for destabilizing Alzheimer’s Aβ42 protofibrils. Med Chem Res 2016; 25: 1616-22.
[http://dx.doi.org/10.1007/s00044-016-1594-y]
[105]
Ahmad J, Akhter S, Rizwanullah M, et al. Nanotechnology based theranostic approaches in Alzheimer’s disease management: Current status and future perspective. Curr Alzheimer Res 2017; 14(11): 1164-81.
[http://dx.doi.org/10.2174/1567205014666170508121031] [PMID: 28482786]
[106]
Li MZ, Zheng LJ, Shen J, et al. SIRT1 facilitates amyloid beta peptide degradation by upregulating lysosome number in primary astrocytes. Neural Regen Res 2018; 13(11): 2005-13.
[http://dx.doi.org/10.4103/1673-5374.239449] [PMID: 30233076]
[107]
Fujita Y, Yamashita T. Sirtuins in neuroendocrine regulation and neurological diseases. Front Neurosci 2018; 12: 778.
[http://dx.doi.org/10.3389/fnins.2018.00778] [PMID: 30416425]
[108]
Martins IJ. Appetite regulation and the peripheral sink amyloid beta clearance pathway in diabetes and Alzheimer’s disease. In: Top 10 Commentaries in Alzheimer’s Disease. Hyderabad: Avid Science 2019; 2: pp. 1-11.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy