摘要
阿尔茨海默病(Alzheimer's disease,AD)是一种以神经系统退行性变为特征的"构象病",淀粉样蛋白Aβ聚集形成富含β折叠的肽类聚合物是其发病机制的核心。不同构象的Aβ肽成分除分子量、溶解性、二级结构等基本性质不同之外,尚有免疫原性、神经细胞毒性等生物学功能的差别。由Aβ构象转变引起的空间结构差异,影响其与生物膜、受体等结合蛋白之间的相互作用,通过不同途径关联到线粒体损伤、神经突触功能异常、早期认知障碍、神经元丢失等病理效应。本文综述了Aβ动态结构特征、Aβ构象转变与神经毒性作用的关系、抑制Aβ构象转变的靶点等,以期为明确构象在AD发病机制中的作用乃至"构象病"的共同机制研究提供新的思路。
Alzheimer＇s disease （AD） is a kind of conformational disease, which is characterized by progressive neurodegeneration. The amyloid β （Aβ） protein aggregation is the center event in AD. Aβ monomers usually turn into β-sheet-rich oligomer, protofibril and fiber. These ＂β structure＂ components are diverse in molecular weight, solubility, immunogenicity and neuronal cytotoxicity. The conformational conversion affects the Aβ-binding ability to receptor and cell membrane. The different Aβ aggregations with distinct content of ＂β structure＂ compositions play different roles in cognitive handicap and neurodegenerative pathogenesis in each period of AD. The most recent progresses in Aβ oligomers generation, assembling, dynamic conformation conversion, the mechanisms in neuronal impairments and factors inhibiting aggregation were summarized in this paper. Perhaps it would provide an approach for developing preclinical diagnosis and therapeutic measures to these kinds of disorders.
出处
《现代生物医学进展》
CAS
2009年第10期1956-1959,1963,共5页
Progress in Modern Biomedicine
基金
国家高技术研究发展计划(No.2006AA02A247)
北京交通大学人才基金(No.2006RC046)
关键词
阿尔茨海默病
淀粉样Β蛋白
构象转变
Alzheimer＇s diseases （AD）
Amyloid β protein
Conformation conversion
