Since the beginning of this century the clinico-pathological focus in Parkinson's disease has been on the substantia nigra. The finding that a shortage of dopamine was the most important factor and that supplementation with dopamine was the answer to many problems for patients, diverted energy from the search for the underlying causative factor.
Why do substantia nigra cells die?
The MPTP story in the early eighties revived the search for causative factors and directed attention to metabolic, mitochondrial, environmental and genetic factors. Mizuno and collaborators did a lot of the pioneeering work, together with some other centers in the world, on unravelling the role of the mitochondria. They showed that mitochondria played an important role, but was the the only contributory factor.