Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases
AbstractAlzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles 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, triggering neurodegeneration according to a cell death matrix theory. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. 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 summarizes how mitochondrial pathobiology might contribute to neuronal death in AD, PD, and ALS and could serve as a target for drug therapy.
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Martin, L.J. Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases. Pharmaceuticals 2010, 3, 839-915.
Martin LJ. Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases. Pharmaceuticals. 2010; 3(4):839-915.Chicago/Turabian Style
Martin, Lee J. 2010. "Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases." Pharmaceuticals 3, no. 4: 839-915.