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What process causes nigral cell death in Parkinson's disease?
P Jenner
Neurol. Clin. 1992 May; 10(2):387-403.
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ABSTRACT
The action of toxins or the altered metabolism of dopamine may lead to
oxidative stress in substantia nigra, thereby inducing dopamine cell death
and the onset of Parkinson's disease. Postmortem studies showing a depletion
of reduced glutathione and increased mitochondrial superoxide dismutase
activity suggest the occurrence of an ongoing toxic process in substantia
nigra involving free radical mechanisms. Indeed there is a selective
impairment of complex I of the mitochondrial respiratory chain in substantia
nigra in Parkinson's disease, mimicking the mode of action of the selective
nigral toxin MPTP.
The increased formation of free radical species in substantia nigra in
patients with Parkinson's disease may be accelerated by an accumulation of
iron within this brain region. Altered iron metabolism and impaired
mitochondrial function are not apparent in the early stages of the illness
and therefore may act as accelerators of some other primary pathologic
process.
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