Calabrese V, Scapagnini G, Giuffrida Stella A M, Bates T E, Clark J B
Department of Chemistry, Faculty of Medicine, University of Catania, Italy.
Neurochem Res. 2001 Jun;26(6):739-64. doi: 10.1023/a:1010955807739.
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.
越来越明显的是，线粒体基因组可能在神经退行性疾病中起关键作用。线粒体功能障碍是几种神经退行性疾病的特征，线粒体是神经退行性疾病损伤部位的证据部分基于帕金森病、阿尔茨海默病和亨廷顿病中呼吸链复合体活性的降低。呼吸复合体活性的这种缺陷可能与氧化/抗氧化平衡紊乱有关，被认为是能量代谢缺陷的基础并诱导细胞变性。维持和修复过程的有效运作似乎对生存和生活质量都至关重要。这是通过一个由所谓的长寿保证过程组成的复杂网络来实现的，这些过程由称为长寿基因的基因组成。应激的类 hormesis 样积极效应代表了一种识别关键衰老过程的有前景的方法。在本综述中，我们讨论了脑线粒体中能量阈值的作用及其在神经退行性变中的意义。然后我们回顾了氧化应激在调节线粒体 DNA 突变对脑年龄相关疾病影响中的作用的证据，并讨论了研究终生生存和长寿机制的新方法。
