Clinical Manifestations and Mechanisms of Action of Environmental Mitochondrial Toxins

There is increasing evidence that defects in mitochondrial energy metabolism play an important role in the pathogenesis of major human neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and dystonia. AD is the most common form of dementia that occurs in the elderly and may result from various genetic and environmental influences (1). A genetic defect arising from mitochondrial DNA (mt DNA) that is inherited solely from the mother could account for defects in the electron transport chain and contributes to deficits in energy levels in AD (2–4). Recent work has shown that mutations in cytochrome c oxidase may impair energy metabolism that may lead to a cascade of events resulting in AD. PD is characterized clinically by bradykinesia, rigidity, and tremors and pathologically by the damage of dopaminergic neurons in the substantia nigra. Some forms of PD are inherited and other forms may be triggered by environmental agents. A significant decrease of mitochondrial complex I activity has been observed in the substantia nigra of Parkinson’s patients (5–8).