Altered mitochondrial function, iron metabolism and glutathione levels in Parkinson's disease.
The mechanisms underlying dopamine cell death in substantia nigra in Parkinson's disease remain unknown. Current concepts of this process suggest the involvement of free radical species and oxidative stress. Indeed, in postmortem tissues from patients dying with Parkinson's disease there is evidence for inhibition of complex I of the mitochondrial respiratory chain, altered iron metabolism and decreased levels of reduced glutathione. However, alterations in iron levels in substantia nigra are not specific to Parkinson's disease but also occur in other basal ganglia degenerative diseases. So, alterations in iron may be a response to, rather than a cause of nigral cell death. This is further suggested by a failure to find any alterations in iron metabolism in cases of incidental Lewy body disease (presymptomatic Parkinson's disease). Similarly, in these tissues no significant alteration in complex I activity is apparent. However, there is a reduction in the levels of reduced glutathione in substantia nigra in incidental Lewy body disease of the same magnitude as occurs in advanced Parkinson's disease. This would suggest that alterations in glutathione function are an early marker of pathology in Parkinson's disease and may be a clue to the primary cause of nigral cell death.
Jenner
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P
Parkinson's Disease Society, King's College London, UK.
D002470:Cell Survival / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology*; D009410:Nerve Degeneration / Q000502:physiology; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D017382:Reactive Oxygen Species; D011954:Receptors, Dopamine / Q000502:physiology; D013378:Substantia Nigra / Q000473:pathology / Q000503:physiopathology
D005609:Free Radicals; D017382:Reactive Oxygen Species; D011954:Receptors, Dopamine; D007501:Iron; D005978:Glutathione; D004298:Dopamine