Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease.
Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease.
复制标题
DOI：
10.1016/j.expneurol.2009.03.042
复制
发表时间：
2009-08
影响因子：
5.3
通讯作者：
Reddy, P. Hemachandra
中科院分区：
文献类型：
--
作者：
Reddy, P. Hemachandra
线粒体是脑细胞正常运作的主要能量来源。越来越多的证据表明，淀粉样前体蛋白（APP）和淀粉样β蛋白（Aβ）在线粒体膜上积聚，导致线粒体结构和功能损伤，并阻止神经元的正常功能。据报道，寡聚体Ab诱导细胞内Ca 2+水平，并促进细胞内Ca 2+过量积聚到线粒体中，诱导线粒体通透性转换孔打开，并破坏线粒体结构。基于最近对APP转基因小鼠和AD死后脑组织基因表达的研究，以及APP/Aβ和线粒体结构的研究，我们认为APP的过度表达和Aβ的产生增加可能导致线粒体结构的改变，包括缺陷线粒体的产生增加，线粒体运输减少，以及AD影响的神经元线粒体动力学的改变。本文就APP/Aβ与AD患者神经元线粒体、线粒体结构和功能损伤以及细胞内钙调节异常的关系进行了讨论。本文还讨论了AD中Aβ与线粒体动力学受损之间的联系。
Mitochondria are the major source of energy for the normal functioning of brain cells. Increasing evidence suggests that the amyloid precursor protein (APP) and amyloid beta (Aβ) accumulate in mitochondrial membranes, cause mitochondrial structural and functional damage, and prevent neurons from functioning normally. Oligomeric Ab is reported to induce intracellular Ca2+ levels and to promote the excess accumulation of intracellular Ca2+ into mitochondria, to induce the mitochondrial permeability transition pore to open, and to damage mitochondrial structure. Based on recent gene expression studies of APP transgenic mice and AD postmortem brains, and APP/Aβ and mitochondrial structural studies, we propose that the overexpression of APP and the increased production of Aβ may cause structural changes of mitochondria, including a increase in the production of defective mitochondria, a decrease in mitochondrial trafficking, and the alteration of mitochondrial dynamics in neurons affected by AD. This article discusses some critical issues of APP/Aβ associated with mitochondria, mitochondrial structural and functional damage, and abnormal intracellular calcium regulation in neurons from AD patients. This article also discusses the link between Aβ and impaired mitochondrial dynamics in AD.
登录
查看更多内容
影响因子：
4.8
作者：
Caspersen, C;Wang, N;Yan, SD
通讯作者：
Yan, SD
影响因子：
5.3
作者：
Crouch, PJ;Blake, R;Trounce, IA
通讯作者：
Trounce, IA
影响因子：
4.8
作者：
Guo, Q;Robinson, N;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
6.1
作者：
Almeida, CG;Tampellini, D;Gouras, GK
通讯作者：
Gouras, GK
影响因子：
11.4
作者：
Barsoum, Mark J.;Yuan, Hua;Bossy-Wetzel, Ella
通讯作者：
Bossy-Wetzel, Ella