Alzheimer氏病淀粉样前体蛋白的研究进展  

Advances in the β Amyloid Precursor Protein of Alzheimers Disease.

作　　者：陈培利[1] 童坦君[1] 张宗玉[1] 

机构地区：[1]北京医科大学生化与分子生物学系

出　　处：《生物化学与生物物理进展》1999年第2期105-108,共4页Progress In Biochemistry and Biophysics

基　　金：国家"九五"老年性痴呆攻关课题

摘　　要：Ａｌｚｈｅｉｍｅｒ氏病（ＡＤ）是一种发生于老年人群的原发性退行性脑病，其特征性病变为细胞内神经纤维缠绕（ＮＦＴ）及细胞外老年斑（ＳＰ）．构成ＳＰ的主要成分β淀粉样多肽（βＡ）为一由淀粉样前体蛋白（ＡＰＰ）剪切而来的分子质量约为４ｋｕ的多肽，其神经毒性可能由其氧化作用和在脂质双层中形成的Ｃａ２＋通道所致．ＡＰＰ的功能目前尚未完全明了，可能具有促进细胞粘附、维护突触膜稳定性等功能．ＡＰＰ主要通过两种途径进行加工修饰：一为分泌途径，由一些假定的分泌酶催化；另一为胞内体溶酶体途径．在形成ＳＰ的βＡ中，较长者比短者更易聚集，因此一些ＡＰＰ突变由于能够释放出更多的较长的βＡ或者使较短的βＡ生成量增加而致发家族性ＡＤ．一些可能在ＡＰＰ的代谢中起着重要作用的因素，如早衰蛋白的突变，也可通过增加βＡ的生成量而致发ＡＤ．Alzheimers disease(AD) is a primary neurodegenerative disorder mainly affecting aged people over 60 years old. It is characterized by extracellular senile plaques(SPs) and intracellular neurofibrillary tangles(NFTs)in patients brains. The major component of SP is β amyloid peptide(βA) with molecular weight of about 4 ku which is a neurotoxic derivative of β amyloid precursor protein(APP) and can cause cell damage mainly through oxidative stress and being able to form calcium channels in lipid bilayers. The precursor, APP, whose function is not yet elucidated in detail but evidence exists that it may mediate cell adhesion, maintain synaptic plasticity and so on, can be processed in conventional secretary way by several putative secretases and alternatively in endosomal/lysosomal way. Longer βA is more predisposed to aggregate to form SP than its shorer counterpart, so some APP mutants may cause familial AD through producing more longer βAs or increasing the production of shorter ones. The changes of some factors which are important for the metabolism of APP, for example, mutations of presenilins, may also cause AD by increased generation of βA.

关 键 词：Β淀粉样 前体蛋白 Β淀粉样多肽 早老性痴呆 

分 类 号：R749.160.2[医药卫生—神经病学与精神病学]