Does mitochondrial respiratory chain dysfunction have a role in common neurodegenerative disorders?

Respiratory chain dysfunction has been established as having a primary pathoaetiological role in certain relatively rare multisystem disorders (typically encephalomyopathies) and postulated as having an important role in commoner neurodegenerative disorders including Alzheimer dementia and Parkinson's disease. In the latter conditions, there is considerable evidence that non-mitochondrial factors have a key role in causation, making it unlikely that respiratory chain failure is the central event in pathoaetiology. Evidence is presented in this paper suggesting a role for mitochondrial dysfunction in upstream events predisposing to neurodegeneration, and in downstream events accelerating cell dysfunction and loss. While probably not having a primary role in pathoaetiology, respiratory chain dysfunction may still be an important risk factor for development of late life neurodegenerative disease and an important effector mechanism in neuronal dysfunction, and therefore represents a legitimate therapeutic target.