This open access paper reviews what is known of the biochemistry of Parkinson's disease. The underlying issue is usually presented as the loss of a small population of dopamine generating neurons. This happens to some degree to everyone over the course of aging; lose enough of these neurons and you will manifest the condition. As to why some people do and some people don't, it's all a question of whether you are inherently more susceptible to the underlying cell death mechanisms, as is the case in a small fraction of the population, or simply through happenstance reach a threshold of loss sufficient to cause symptoms. The question proposed here is whether loss of neurons is all that is going on, or whether the many other changes that occur with aging are also necessary for the development of Parkinson's as a disease:
It is generally considered that Parkinson's disease (PD) is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for PD. Neurons degenerating in PD also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations.
However, reviewed data suggest that PD may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. PD is the result of the slow neurodegenerative action of aging, an effect that can be accelerated by repeated damage to dopaminergic neurons accumulated over a person's lifespan. When the dopaminergic neurons degeneration reaches a critical level and the compensatory mechanisms are insufficient to maintain the basic functions of dopamine, the first motor disturbances appear and the diagnosis of PD can be made. Thus, the etiologic agents involved in PD could be the same as those involved in aging.
The action of these agents could be particularly important in dopaminergic neurons because of their high vulnerability to age-related agents and because these cells are highly susceptible to a number of silent toxics. This could explain why 50 years after first finding of dopaminergic neuron degeneration in sporadic PD, no specific causes for this illness have yet been found. In our opinion, more direct attention to the aging processes could accelerate the acquisition of new knowledge on the biological basis of PD, and actions aimed at delaying aging or promoting rejuvenation could also be useful to control the onset and progression of PD.