MPTP, itself, is not a neurotoxin -- it first must be converted to to 1-methyl-4-phenylpyridine (MPP) by the enzyme monoamine oxidase B. MPP is a byproduct of dopamine synthesis in substantia nigral cells. MPP can cause cellular death by disrupting mitochondrial metabolism, which can result in the depletion of cellular energy, or ATP, and intracellular calcium content. The maintenance of intracellular calcium is crucial because too much calcium can lead to programmed cell death. Moreover, MPP can induce lipid membrane destruction by the formation of free radicals. However, normally, there is a large presence of enzymes, such as superoxide dimutase and glutathione peroxidase, which neutralizes this effect. In Parkinson's patients, there is a decreased number of glutathione peroxidase.
In the substantia nigra, free radicals are also formed by monoamine oxidase B during dopamine catabolism. Normally, neurons are protected by enzymes and free radical scavengers. However, with the aging process, these "protectors" are reduced and consequently, neurons die.
Another characteristic of PD is the presence of Lewy bodies (Marsden, 952). These are inclusions which are found throughout the brain. Lewy bodies are also found in the elderly who are symptom-free of PD and in some patients with Alzheimer's disease. Excess iron has been linked to the number of Lewy bodies, but the exact reason for their existence is still unknown.