Mitochondrial involvement in brain function and dysfunction: Relevance to aging, neurodegenerative disorders and longevity

被引:209
作者
Calabrese, V
Scapagnini, G
Stella, AMG
Bates, TE
Clark, JB
机构
[1] Univ Catania, Fac Med, Dept Chem, Sect Biochem & Mol Biol, I-95100 Catania, Italy
[2] UCL, Inst Neurol, Dept Neurochem, London WC1N 3BG, England
基金
英国惠康基金;
关键词
oxidative stress; mitochondrial diseases; energy thresholds; caloric restriction; vitagenes;
D O I
10.1023/A:1010955807739
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is becoming increasingly evident that the mitochondrial genome may play a key role in neurodegenerative diseases. Mitochondrial dysfunction is characteristic of several neurodegenerative disorders, and evidence for mitochondria being a site of damage in neurodegenerative disorders is partially based on decreases in respiratory chain complex activities in Parkinson's disease. Alzheimer's disease, and Huntington's disease. Such defects in respiratory complex activities, possibly associated with oxidant/antioxidant balance perturbation. are thought to underlie defects in energy metabolism and induce cellular degeneration. Efficient functioning of maintenance and repair process seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes. which are composed of genes termed vitagenes. A promising approach for the identification of critical gerontogenic processes is represented by the hormesis-like positive effect of stress, In the present review, we discuss the role of energy thresholds in brain mitochondria and their implications in neurodegeneration. We then review the evidence for the role of oxidative stress in modulating the effects of mitochondrial DNA mutations on brain age-related disorders and also discuss new approaches for investigating the mechanisms of lifetime survival and longevity.
引用
收藏
页码:739 / 764
页数:26
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