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Beta淀粉样多肽的高分辨结构解析 被引量：3

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摘要 β淀粉样蛋白(β-amyloid protein,Aβ)在阿尔茨海默病(Alzheimer's disease,AD)的发生和发展过程中起着关键作用。Aβ单体在体内会聚集形成各种尺寸和形貌的聚集体,沉淀在神经细胞表面,形成淀粉样斑块,导致神经细胞的功能障碍甚至是死亡。由于Aβ分子及其组装体的组装结构对于理解AD的发生、发展过程以及致病机制都至关重要,研究者们致力于利用X射线衍射、核磁共振谱、电子显微镜、傅立叶变换红外光谱、圆二色谱和扫描隧道显微技术等方法来研究Aβ的分子结构及组装结构。研究表明,Aβ中富含β-折叠链结构,存在由一个或若干个β-转角或环连接的β-折叠链,其中具有代表性的是发卡型的β-折叠链结构。在形成纤维的过程中,相邻β-折叠链之间靠侧链间、主链间的氢键作用形成平行排列的β-片层结构;稳定分子内结构的作用力主要为侧链间的疏水相互作用和带电氨基酸残基间的静电相互作用。Aβ分子结构及组装结构的研究有助于阐明Aβ的聚集、AD的发病机制,对于AD的早期预防、诊断和治疗具有非常重要的意义。
作者 徐萌 杨延莲 王琛
机构地区 国家纳米科学中心
出处 《东南大学学报（医学版）》 CAS 2011年第1期228-240,共13页 Journal of Southeast University(Medical Science Edition)
基金 国家自然科学基金资助项目(20911130229) 国家重大科学研究计划项目("973"项目)(2009CB930100) 中国科学院重要方向项目(KJCX2-YW-M15)
关键词 Β淀粉样蛋白 β-折叠链 组装体 扫描隧道显微技术 文献综述
分类号 Q6-3 [生物学—生物物理学]
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参考文献75

  • 1ROBERSON E D,MUCKE L.100 years and counting:prospects for defeating Alzheimer's disease[J].Science,2006,314(5800):781-784.
  • 2GOATE A.Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease[J].Journal of Alzheimer's Disease,2006,9(3):341-347.
  • 3KIRSCHNER D A,INOUYE H,DUFFY L K,et al.Synthetic peptide homologous to beta-protein from Alzheimer-disease forms amyloid-like fibrils in vitro[J].Proc Natl Acad Sci USA,1987,84(19):6953-6957.
  • 4KELENYI G.Thioflavin S fluorescent and congo red anisotropic stainings in histologic demonstration of amyloid[J].Acta Neuropathologica,1967,7(4):336-348.
  • 5IWATSUBO T,ODAKA A,SUZUKI N,et al.Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals:evidence that an initially deposited species is Aβ42(43)[J].Neuron,1994,13(1):45-53.
  • 6IWATSUBO T,MANN D M A,ODAKA A,et al.Amyloid protein (Aβ) deposition:Aβ42(43) precedes Aβ40 in Down syndrome[J].Ann Neurol,1995,37(3):294-299.
  • 7VASSAR R,BENNETT B D,BABU-KHAN S,et al.β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE[J].Science,1999,286(5440):735-741.
  • 8PUGLIELLI L,TANZI R E,KOVACS D M.Alzheimer's disease:the cholesterol connection[J].Nat Neurosci,2003,6:345-351.
  • 9DAVIS J,van NOSTRAND W E.Enhanced pathologic properties of Dutch-type mutant amyloid β-protein[J].Proc Natl Acad Sci USA,1996,93(7):2996-3000.
  • 10JARRETT J T,LANSBURY P T Jr.Seeding "one-dimensional crystallization" of amyloid:a pathogenic mechanism in Alzheimer's disease and scrapie?[J] Cell,1993,73(6):1055-1058.

同被引文献35

  • 1ANEKONDA T S, QUINN J F, HARRIS C, et al. L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer's disease [ J ]. Neurobiol Dis, 2011, 41(1) :62-70.
  • 2XU F,CRANDE A M, ROBINSON J K, et al. Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid betaprotein precursor transgenic mice [ J ]. Neuroscience, 2007,146(1) : 98-107.
  • 3PAXINOS G, WATSON C. The rat brain: in stereotaxic coordinates [ M ]. 6th edition. London : Elsevier Academic, 2004 : 48-123.
  • 4van DAM D, de DEYN P P. Animal models in the drug discovery pipeline for Alzheimer's disease [ J ]. Br J Pharmacol, 2011, Mar 3. 1476-5381.
  • 5CLEMENTI M E, MARINI S, COLETYA M, et al. Aβ(3135 ) and AI3( 25-35 ) fragments of amyloid beta-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35 [ J ]. FEBS Lett,2005,579 ( 13 ) : 2913-2918.
  • 6FROZZA R L, HORN A P, HOPPE J B, et al. A comparative study of beta-amyloid peptides Abetal-42 and Abeta25-35 toxicity in organotypic hippocampal slice cultures [ J ]. Neurochem Res,2009,34 (2) : 295-303.
  • 7LIM6N I D, DfAZ A, MENDIETA L, et al. Amyloid-beta (25-35) impairs memory and increases NO in the temporal cortex of rats[J]. Neurosei Res,2009,63(2) :129-137.
  • 8DIAZ A, MENDIETA L, ZENTENO E, et al. The role of NOS in the impairment of spatial memory and damaged neurons in rats injected with amyloid beta 25-35 into the temporal cortex[J]. Pharmacol Biochem Behav, 2011, 98( 1 ) : 67-75.
  • 9LEONI V. The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease [ J ]. Clin Chem Lab Med, 2011,49(3) :375-383 .
  • 10HENRY W, FRANK M. Mechanisms of disease Alzheimer's disease[J]. N Engl J Med,2010;362(4) :329-344.

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东南大学学报（医学版）
2011年 第1期

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