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A major theory regarding the mechanism of neuronal degeneration in several movement disorders is that mitochondrial defects may play a role. Biochemical studies in Parkinson's disease, Huntington's disease, multiple system atrophy, and idiopathic dystonia have shown defects in enzymes of oxidative phosphorylation in postmortem brain tissue, platelets, muscle, or lymphocytes. The basal ganglia and substantia nigra are also particularly susceptible to the accumulation of age-dependent mitochondrial DNA deletions, which may contribute to the delayed onset of movement disorders. The 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine model of Parkinson's disease involves conversion to 1-methyl-4-phenylpyridinium, which then inhibits complex I of the electron transport chain. Our studies show that the complex II inhibitor 3-nitropropionic acid can closely replicate the neurochemical, histologic, and clinical features of Huntington's disease. The mechanism of neuronal death in both these models may be slow excitotoxicity. Both direct biochemical studies and animal models of movement disorders therefore suggest that mitochondrial dysfunction may play a direct role in their pathogenesis.
Schulz et al. (Mon,) studied this question.