Y. Mizuno et al., ROLE OF MITOCHONDRIA IN THE ETIOLOGY AND PATHOGENESIS OF PARKINSONS-DISEASE, Biochimica et biophysica acta. Molecular basis of disease, 1271(1), 1995, pp. 265-274
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.