Mitochondrial pathobiology in Parkinson's disease and amyotrophic lateral sclerosis.
Mitochondrial pathobiology in Parkinson's disease and amyotrophic lateral sclerosis.
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DOI：
10.3233/jad-2010-100348
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发表时间：
2010-06
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影响因子：
--
通讯作者：
L. Martin
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文献类型：
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作者：
L. Martin
帕金森病（PD）和肌萎缩侧索硬化症（ALS）分别是继阿尔茨海默病之后第二和第三大最常见的人类成人神经退行性疾病。他们的特点是在选择性脆弱的神经系统中突出的与年龄相关的神经变性。某些形式的PD和ALS是遗传的，引起这些疾病的基因已经被确定。形态学、生物化学、遗传学以及细胞和动物模型的研究表明，线粒体可能在这种神经变性中起作用。线粒体的功能和特性可能使选择性脆弱的神经元亚群本质上容易受到细胞衰老和压力以及覆盖的遗传变异的影响。在帕金森病中，已知线粒体蛋白发生突变，在黑质神经元中发现线粒体DNA突变。ALS患者线粒体呼吸链酶和线粒体细胞死亡蛋白发生变化。人类神经退行性疾病的转基因小鼠模型开始揭示可能的原则，调控选择性神经元易感性的生物学，涉及线粒体和线粒体通透性过渡孔。这篇综述将介绍线粒体病理生物学如何有助于PD和ALS的神经退行性变，并可能作为药物治疗的靶点。
Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are the second and third most common human adult-onset neurodegenerative diseases, respectively, after Alzheimer's disease. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of PD and ALS are inherited, and genes causing these diseases have been identified. Morphological, biochemical, and genetic, as well as cell and animal model, studies reveal that mitochondria could have a role in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations. In PD, mutations in putative mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This review will present how mitochondrial pathobiology might contribute to neurodegeneration in PD and ALS and could serve as a target for drug therapy.