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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

假蒟通过抑制SH-SY5Y细胞中的淀粉样蛋白形成和Tau蛋白过磷酸化来减少β -淀粉样蛋白(Aβ)诱导的神经毒性

卷 18, 期 1, 2021

发表于: 24 March, 2021

页: [80 - 87] 页: 8

弟呕挨: 10.2174/1567205018666210324124239

价格: $65

摘要

背景：在阿尔茨海默病中，β淀粉样蛋白(Aβ)的积累触发淀粉样蛋白的形成和 Tau蛋白的过度磷酸化导致神经元细胞死亡。假蒟（PS）是马来人常用的一种传统草药，用于治疗风湿、头痛和增强记忆力。它具有抗胆碱能、抗炎、抗氧化、抗抑郁等多种生物学作用。 目的：本研究旨在探讨PS对Aβ诱导的神经毒性的保护作用，并探讨其潜在的作用机制。 方法：研究了PS叶(L)和根(R)的正己烷(HXN)、二氯甲烷(DCM)、乙酸乙酯(EA)和甲醇(MEOH)提取物对Aβ诱导的人神经母细胞瘤细胞的神经保护作用。PS预处理24 h后，Aβ诱导24 h。采用细胞活力和细胞活性氧(ROS)测定方法研究了PS的神经保护作用。测定细胞外Aβ和Tau蛋白的苏氨酸231 (pT231)磷酸化水平。分别使用qRT-PCR和western blot分析基因和蛋白表达。 结果：PS (LHXN和RHXN)的己烷提取物可以保护SH-SY5Y细胞免受Aβ诱导的神经毒性，并降低细胞外Aβ和磷酸化Tau蛋白(pT231)的水平。虽然PS的提取物抑制β全身的活性氧产量,但不太可能具有神经保护效应，只是由于PS进一步的抗氧化能力,机械性的研究表明PS的神经保护作用可能是由于其通过下调BACE和APP来调节淀粉样生成的能力。 结论：这些发现表明，PS的己烷提取物通过减少淀粉样蛋白的形成和Tau蛋白的过度磷酸化，对SH-SY5Y细胞的Aβ诱导的神经毒性具有神经保护作用。由于其神经保护功能，PS可能是一种潜在的治疗阿尔茨海默病的药物。

关键词: 假蒟，阿尔兹海默症，β-淀粉样蛋白，Tau过度磷酸化，淀粉样蛋白形成，神经保护

« Previous
[1]
Nisbet RM, Polanco JC, Ittner LM, Götz J. Tau aggregation and its interplay with amyloid-β. Acta Neuropathol 2015; 129(2): 207-20.
[http://dx.doi.org/10.1007/s00401-014-1371-2] [PMID: 25492702]
[2]
Spires-Jones TL, Hyman BT. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 2014; 82(4): 756-71.
[http://dx.doi.org/10.1016/j.neuron.2014.05.004] [PMID: 24853936]
[3]
Schmid S, Jungwirth B, Gehlert V, et al. Intracerebroventricular injection of beta-amyloid in mice is associated with long-term cognitive impairment in the modified hole-board test. Behav Brain Res 2017; 324: 15-20.
[http://dx.doi.org/10.1016/j.bbr.2017.02.007] [PMID: 28193522]
[4]
Cai Z, Hussain MD, Yan LJ. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease. Int J Neurosci 2014; 124(5): 307-21.
[http://dx.doi.org/10.3109/00207454.2013.833510] [PMID: 23930978]
[5]
Mao P, Reddy PH. Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer’s disease: Implications for early intervention and therapeutics. Biochim Biophys Acta 2011; 1812(11): 1359-70.
[http://dx.doi.org/10.1016/j.bbadis.2011.08.005] [PMID: 21871956]
[6]
Mondragón-Rodríguez S, Perry G, Zhu X, Boehm J. Amyloid Beta and tau proteins as therapeutic targets for Alzheimer’s disease treatment: Rethinking the current strategy. Int J Alzheimers Dis 2012; 2012: 630182.
[http://dx.doi.org/10.1155/2012/630182] [PMID: 22482074]
[7]
Zhang H, Ma Q, Zhang YW, Xu H. Proteolytic processing of Alzheimer’s β-amyloid precursor protein. J Neurochem 2012; 120(Suppl. 1): 9-21.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07519.x] [PMID: 22122372]
[8]
Zhang Z, Song M, Liu X, et al. Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer’s disease. Nat Commun 2015; 6: 8762.
[http://dx.doi.org/10.1038/ncomms9762] [PMID: 26549211]
[9]
Ma T, Tan MS, Yu JT, Tan L. Resveratrol as a therapeutic agent for Alzheimer’s disease. BioMed Res Int 2014; 2014: 350516.
[http://dx.doi.org/10.1155/2014/350516] [PMID: 25525597]
[10]
Wang YP, Wang XC, Tian Q, et al. Endogenous overproduction of β-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in N2a cells. J Neural Transm (Vienna) 2006; 113(11): 1723-32.
[http://dx.doi.org/10.1007/s00702-006-0507-5] [PMID: 16752046]
[11]
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]
[12]
Stancu IC, Vasconcelos B, Terwel D, Dewachter I. Models of β-amyloid induced Tau-pathology: The long and “folded” road to understand the mechanism. Mol Neurodegener 2014; 9: 51.
[http://dx.doi.org/10.1186/1750-1326-9-51] [PMID: 25407337]
[13]
Asuni AA, Guridi M, Pankiewicz JE, Sanchez S, Sadowski MJ. Modulation of amyloid precursor protein expression reduces β-amyloid deposition in a mouse model. Ann Neurol 2014; 75(5): 684-99.
[http://dx.doi.org/10.1002/ana.24149] [PMID: 24687915]
[14]
Šimić G, Babić Leko M, Wray S, et al. Tau protein hyperphosphorylation and aggregation in Alzheimer’s disease and other tauopathies, and possible neuroprotective strategies. Biomolecules 2016; 6(1): 6.
[http://dx.doi.org/10.3390/biom6010006] [PMID: 26751493]
[15]
Hematpoor A, Liew SY, Chong WL, Azirun MS, Lee VS, Awang K. Inhibition and larvicidal activity of phenylpropanoids from Piper sarmentosum on acetylcholinesterase against mosquito vectors and their binding mode of interaction. PLoS One 2016; 11(5): e0155265.
[http://dx.doi.org/10.1371/journal.pone.0155265] [PMID: 27152416]
[16]
Zakaria ZA, Patahuddin H, Mohamad AS, Israf DA, Sulaiman MR. In vivo anti-nociceptive and anti-inflammatory activities of the aqueous extract of the leaves of Piper sarmentosum. J Ethnopharmacol 2010; 128(1): 42-8.
[http://dx.doi.org/10.1016/j.jep.2009.12.021] [PMID: 20035852]
[17]
Amran AA, Zakaria Z, Othman F, Das S, Al-Mekhlafi HM, Nordin NAM. Changes in the vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and c-reactive protein following administration of aqueous extract of piper sarmentosum on experimental rabbits fed with cholesterol diet. Lipids Health Dis 2011; 10: 2.
[http://dx.doi.org/10.1186/1476-511X-10-2] [PMID: 21214952]
[18]
Mohd Zainudin M, Zakaria Z, Megat Mohd Nordin NA. The use of Piper sarmentosum leaves aqueous extract (Kadukmy™) as antihypertensive agent in spontaneous hypertensive rats. BMC Complement Altern Med 2015; 15: 54.
[http://dx.doi.org/10.1186/s12906-015-0565-z] [PMID: 25887182]
[19]
Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disorder 2013; 6(1): 19-33.
[http://dx.doi.org/10.1177/1756285612461679] [PMID: 23277790]
[20]
Li Q, Qu FL, Gao Y, et al. Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity. J Ethnopharmacol 2017; 199: 9-19.
[http://dx.doi.org/10.1016/j.jep.2017.01.037] [PMID: 28126450]
[21]
Khan M, Elhussein SAA, Khan MM, Khan N. Anti-acetylcholinesterase activity of Piper sarmentosum by a continuous immobilized-enzyme assay. APCBEE Procedia 2012; 2: 199-204.
[http://dx.doi.org/10.1016/j.apcbee.2012.06.035]
[22]
Jiang B, Wang F, Yang S, et al. SKF83959 produces antidepressant effects in a chronic social defeat stress model of depression through BDNF-TrkB pathway. Int J Neuropsychopharmacol 2014; 18(6): 6.
[http://dx.doi.org/10.1093/ijnp/pyu096] [PMID: 25522427]
[23]
Pan XD, Zhu YG, Lin N, et al. Microglial phagocytosis induced by fibrillar β-amyloid is attenuated by oligomeric β-amyloid: implications for Alzheimer’s disease. Mol Neurodegener 2011; 6: 45.
[http://dx.doi.org/10.1186/1750-1326-6-45] [PMID: 21718498]
[24]
Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY, Chan EWL. Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells. J Ethnopharmacol 2018; 217: 187-94.
[http://dx.doi.org/10.1016/j.jep.2018.02.025] [PMID: 29462698]
[25]
Chan EWL, Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY. Piper sarmentosum Roxb. root extracts confer neuroprotection by attenuating beta-amyloid-induced pro-inflammatory cytokines released from microglial cells. Curr Alzheimer Res 2019; 16(3): 251-60.
[http://dx.doi.org/10.2174/1567205016666190228124630] [PMID: 30819080]
[26]
Hussain K, Hashmi FK, Latif A, Ismail Z, Sadikun A. A review of the literature and latest advances in research of Piper sarmentosum. Pharm Biol 2012; 50(8): 1045-52.
[http://dx.doi.org/10.3109/13880209.2011.654229] [PMID: 22486533]
[27]
Brimson JM, Brimson SJ, Brimson CA, Rakkhitawatthana V, Tencomnao T. Rhinacanthus nasutus extracts prevent glutamate and amyloid-β neurotoxicity in HT-22 mouse hippocampal cells: Possible active compounds include lupeol, stigmasterol and β-sitosterol. Int J Mol Sci 2012; 13(4): 5074-97.
[http://dx.doi.org/10.3390/ijms13045074] [PMID: 22606031]
[28]
Gu MY, Kim J, Yang HO. The neuroprotective effects of Justicidin A on amyloid beta25–35-induced neuronal cell death through inhibition of tau hyperphosphorylation and induction of autophagy in SH-SY5Y Cells. Neurochem Res 2016; 41(6): 1458-67.
[http://dx.doi.org/10.1007/s11064-016-1857-5] [PMID: 26887582]
[29]
Oguchi T, Ono R, Tsuji M, et al. Cilostazol suppresses Aβ-induced neurotoxicity in SH-SY5Y cells through inhibition of oxidative stress and MAPK signaling pathway. Front Aging Neurosci 2017; 9: 337.
[http://dx.doi.org/10.3389/fnagi.2017.00337] [PMID: 29089887]
[30]
Ugusman A, Zakaria Z, Hui CK, Nordin NAMM, Mahdy ZA. Flavonoids of Piper sarmentosum and its cytoprotective effects against oxidative stress. EXCLI J 2012; 11: 705-14.
[PMID: 27847456]
[31]
Mansuri ML, Parihar P, Solanki I, Parihar MS. Flavonoids in modulation of cell survival signalling pathways. Genes Nutr 2014; 9(3): 400.
[http://dx.doi.org/10.1007/s12263-014-0400-z] [PMID: 24682883]
[32]
Hafizah AH, Zaiton Z, Zulkhairi A, Mohd Ilham A, Nor Anita MM, Zaleha AM. Piper sarmentosum as an antioxidant on oxidative stress in human umbilical vein endothelial cells induced by hydrogen peroxide. J Zhejiang Univ Sci B 2010; 11(5): 357-65.
[http://dx.doi.org/10.1631/jzus.B0900397] [PMID: 20443214]
[33]
Lefort R, Pozueta J, Shelanski M. Cross-linking of cell surface APP leads to increased Aβ production in hippocampal neurons: Implications for Alzheimer’s disease. J Neurosci 2012; 32: 10674-85.
[http://dx.doi.org/10.1523/JNEUROSCI.6473-11.2012] [PMID: 22855816]
[34]
Mockett BG, Richter M, Abraham WC, Müller UC. Therapeutic potential of secreted amyloid precursor protein APPsα. Front Mol Neurosci 2017; 10: 30.
[http://dx.doi.org/10.3389/fnmol.2017.00030] [PMID: 28223920]
[35]
Hung SY, Huang WP, Liou HC, Fu WM. Autophagy protects neuron from Abeta-induced cytotoxicity. Autophagy 2009; 5(4): 502-10.
[http://dx.doi.org/10.4161/auto.5.4.8096] [PMID: 19270530]
[36]
Qi HS, Liu P, Gao SQ, et al. Inhibitory effect of piperlonguminine/ dihydropiperlonguminine on the production of amyloid β and APP in SK-N-SH cells. Chin J Physiol 2009; 52(3): 160-8.
[http://dx.doi.org/10.4077/CJP.2009.AMH062] [PMID: 19777802]
[37]
Adesina SK, Adebayo AS, Adesina SK, Gröning R. New constituents of Piper guineense fruit and leaf. Pharmazie 2003; 58(6): 423-5.
[http://dx.doi.org/10.1002/chin.200340213] [PMID: 12857009]
[38]
Zhu Z, Yan J, Jiang W, et al. Arctigenin effectively ameliorates memory impairment in Alzheimer’s disease model mice targeting both β-amyloid production and clearance. J Neurosci 2013; 33(32): 13138-49.
[http://dx.doi.org/10.1523/JNEUROSCI.4790-12.2013] [PMID: 23926267]
[39]
Kirouac L, Rajic AJ, Cribbs DH, Padmanabhan J. Activation of RAS-ERK signaling and GSK-3 by amyloid precursor protein and amyloid beta facilitates neurodegeneration in Alzheimer’s disease. eNeuro 2017; 4(2): ENEURO.0149-.
[40]
Schwalbe M, Kadavath H, Biernat J, et al. Structural impact of tau phosphorylation at threonine 231. Structure 2015; 23(8): 1448-58.
[http://dx.doi.org/10.1016/j.str.2015.06.002] [PMID: 26165593]
[41]
Giraldo E, Lloret A, Fuchsberger T, Viña J. Aβ and tau toxicities in Alzheimer’s are linked via oxidative stress-induced p38 activation: protective role of vitamin E. Redox Biol 2014; 2: 873-7.
[http://dx.doi.org/10.1016/j.redox.2014.03.002] [PMID: 25061569]
[42]
Moore S, Evans LDB, Andersson T, et al. APP metabolism regulates tau proteostasis in human cerebral cortex neurons. Cell Rep 2015; 11(5): 689-96.
[http://dx.doi.org/10.1016/j.celrep.2015.03.068] [PMID: 25921538]

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