期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 171, 期 8, 页码 1943-1957出版社
WILEY
DOI: 10.1111/bph.12433
关键词
mitochondria; Parkinson's disease; mitophagy; free radicals; respiratory chain; PINK1; PARKIN; oxidative stress; calcium
资金
- MRC [MC_U132674518] Funding Source: UKRI
- Medical Research Council [MC_U132674518] Funding Source: Medline
- Academy of Medical Sciences (AMS) [AMS-SGCL5-Gandhi] Funding Source: researchfish
- Medical Research Council [MC_U132674518] Funding Source: researchfish
- Wellcome Trust [100172/Z/12/Z] Funding Source: researchfish
- Wellcome Trust [100172/Z/12/Z] Funding Source: Wellcome Trust
Mitochondria are essential for cellular function due to their role in ATP production, calcium homeostasis and apoptotic signalling. Neurons are heavily reliant on mitochondrial integrity for their complex signalling, plasticity and excitability properties, and to ensure cell survival over decades. The maintenance of a pool of healthy mitochondria that can meet the bioenergetic demands of a neuron, is therefore of critical importance; this is achieved by maintaining a careful balance between mitochondrial biogenesis, mitochondrial trafficking, mitochondrial dynamics and mitophagy. The molecular mechanisms that underlie these processes are gradually being elucidated. It is widely recognized that mitochondrial dysfunction occurs in many neurodegenerative diseases, including Parkinson's disease. Mitochondrial dysfunction in the form of reduced bioenergetic capacity, increased oxidative stress and reduced resistance to stress, is observed in several Parkinson's disease models. However, identification of the recessive genes implicated in Parkinson's disease has revealed a common pathway involving mitochondrial dynamics, transport, turnover and mitophagy. This body of work has led to the hypothesis that the homeostatic mechanisms that ensure a healthy mitochondrial pool are key to neuronal function and integrity. In this paradigm, impaired mitochondrial dynamics and clearance result in the accumulation of damaged and dysfunctional mitochondria, which may directly induce neuronal dysfunction and death. In this review, we consider the mechanisms by which mitochondrial dysfunction may lead to neurodegeneration. In particular, we focus on the mechanisms that underlie mitochondrial homeostasis, and discuss their importance in neuronal integrity and neurodegeneration in Parkinson's disease. Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据