ROLE OF MITOCHONDRIA IN THE ETIOLOGY AND PATHOGENESIS OF PARKINSONS-DISEASE

We discuss the etiology and pathogenesis of Parkinson's disease (PD). Our group and others have found a decrease in complex I of the mitocho ndrial electron transfer complex in the substantia ni,ora of patients with PD; in addition, we reported loss of the alpha-ketoglutarate dehy drogenase complex (KGDHC) in the substantia nigra. Dual loss of comple x I and the KGDHC will deleteriously affect the electron transport and ATP synthesis; we believe that energy crisis is the most important me chanism of nigral cell death in PD. Oxidative stress has also been imp licated as an important contributor to nigral cell death in PD, but we believe that oxidative stress is a secondary phenomenon to respirator y failure, because respiratory failure will increase oxygen free-radic al formation and consume glutathione. The primary cause of mitochondri al respiratory failure has not been elucidated yet, but additive effec t of environmental neurotoxins in genetically predisposed persons appe ars to be the most likely possibility.