《生命科学》 2008, 20(4):

b-淀粉样肽的细胞内毒性与线粒体通透性转变孔道

郑春艳，章海燕，唐希灿*

（中国科学院上海药物研究所 新药研究国家重点实验室，上海 201203）

摘　要：摘　要：b-淀粉样肽(amyloid-b peptide, Ab)是阿尔采末病患者脑内老年斑的主要成分，具有很强的神经毒性。近年来，研究发现细胞内产生和聚集的Ab可以通过多种途径发挥其神经毒性作用。利用离体线粒体模型发现，Ab可以导致线粒体通透性转变孔道(mitochondrial permeability transition pore, MPTP)开放。MPTP开放会进一步加剧线粒体功能的损伤，并可导致细胞色素c和凋亡诱导因子释放，在线粒体介导的细胞死亡中具有重要作用。Ab引起的MPTP开放可能是胞内Ab导致神经元死亡的重要通路，研究Ab对该孔道的影响将有助于阐明Ab的毒性机理并以期找到减轻Ab损伤的新策略。
关键词：阿尔采末病；b-淀粉样肽；线粒体；线粒体通透性转变孔道
中图分类号：R749.1；Q244　　文献标识码：A

Toxicity of intracellular amyloid-b peptide and mitochondrial permeability transition pore

ZHENG Chun-yan, ZHANG Hai-yan, TANG Xi-can*

(State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China)

Abstract: Abstract: Amyloid-b (Ab), the main constituent of senile plaques in the brain of Alzheimer‘s disease (AD) patients, has been demonstrated to be neurotoxic both in vivo and in vitro. Recently, intracellular Ab has been widely found to exert its neurotoxicity through multiple pathways. Accumulating studies, based on the isolated mitochondria, have reported that Ab could induce the opening of mitochondrial permeability transition pore (MPTP), aggravate mitochondrial dysfunction, and eventually result in the release of cytochrome c and apoptosis-inducing-factor from mitochondria, which may underlie the mechanisms of intracellular Ab induced neurotoxicity. Efforts on elucidating MPTP involvement in Ab action are anticipated to be helpful to find new ways attenuating Ab-induced neurotoxicity.
Key words: Alzheimer’s disease; amyloid-b peptide; mitochondria; mitochondrial permeability transition pore