Mitochondrial dynamics in Alzheimer's disease: opportunities for future treatment strategies.
Mitochondrial dynamics in Alzheimer's disease: opportunities for future treatment strategies.
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DOI：
10.2165/11532140-000000000-00000
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发表时间：
2010-03-01
期刊：
影响因子：
2.8
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Bonda DJ;Wang X;Perry G;Smith MA;Zhu X
阿尔茨海默病的认知障碍和神经变性特征的复杂性尚未完全理解，尽管已经确定了疾病发病机制中的许多因素。在疾病发展中特别重要的似乎是线粒体紊乱。作为细胞代谢中的关键角色，线粒体与细胞存活有关，因此任何偏离其运作的行为都是致命的。在这篇综述中，我们描述了如何线粒体分裂和融合的动态平衡，特别是细胞增殖的一个必要方面，随着细胞的年龄，这种平衡不可避免地受到损害，产生一个破坏性的环境中，细胞不能存在。这种紊乱的证据在阿尔茨海默病中是丰富的。也就是说，AD中裂变和融合的动态平衡大大转向裂变，因此，受影响的神经元含有无法满足细胞代谢需求的异常线粒体。此外，AD细胞中的线粒体分布是核周的，在远端过程中几乎没有代谢细胞器，在远端过程中它们通常分布在健康细胞中，并且在远端过程中它们是胞吐、离子通道泵和突触功能等所需要的。因此，AD神经元的特征在于反应性氧化物质的增加和代谢能力的降低，值得注意的是，这些变化在AD进展的早期就很明显。因此，我们认为，氧化应激和改变线粒体动力学有助于沉淀的AD病理，从而认知能力下降。这些影响为治疗干预提供了一个窗口（即，线粒体保护），如果充分开发，则具有显著阻止AD进展的潜力。本文描述了目前正在调查的治疗策略。
The complexities that underlie the cognitive impairment and neurodegeneration characteristic of Alzheimer's disease have yet to be completely understood, although many factors in disease pathogenesis have been identified. Particularly important in disease development seem to be mitochondrial disturbances. As pivotal role players in cellular metabolism, mitochondria are pertinent to cell survival and thus any deviation from their operation is certainly fatal. In this review, we describe how the dynamic balance of mitochondrial fission and fusion in particular is a necessary aspect of cell proliferation and that, as the cell ages, such balance is inevitably compromised to yield a destructive environment in which the cell cannot exist. Evidence for such disturbance is abundant in Alzheimer disease. That is, the dynamic balance of fission and fusion in AD is greatly shifted toward fission, and, as a result, affected neurons contain abnormal mitochondria that are unable to meet the metabolic demands of the cell. Moreover, mitochondrial distribution in AD cells is perinuclear, with few metabolic organelles in the distal processes where they are normally distributed in healthey cells and where they are needed for exocytosis, ion channel pumps, and synaptic function, among other things. AD neurons are thus characterized by increases in reactive oxidative species and decreases in metabolic capability, and notably, these changes are evident very early in AD progression. We therefore believe that oxidative stress and altered mitochondrial dynamics contribute to the precipitation of AD pathology and thus cognitive decline. These implications provide a window for therapeutic intervention (i.e., mitochondrial protection) that has the potential to significantly deter AD progression if adequately developed. Current treatment strategies under investigation are herein described.
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影响因子：
9.2
作者：
De Vos, KJ;Allan, VJ;Sheetz, MP
通讯作者：
Sheetz, MP
影响因子：
21.3
作者：
Bleazard, W;McCaffery, JM;Shaw, JM
通讯作者：
Shaw, JM
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
4.7
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA
影响因子：
4
作者：
Benard, Giovanni;Bellance, Nadege;Rossignol, Rodrigue
通讯作者：
Rossignol, Rodrigue