Oxidative stress in Parkinson's disease and other neurodegenerative disorders.
The cause of cell death in neurodegenerative diseases remains unknown but the formation of free radicals and the occurrence of oxidative stress may be a common component of many, if not all, such disorders. For example, in substantia nigra in Parkinson's diseases key alterations occur, in iron handling, mitochondrial function and antioxidant defences, particularly reduced glutathione. These indices of oxidative stress are accompanied by evidence of free radical mediated damage in the form of increased lipid peroxidation and oxidation of DNA bases. The alterations in oxidative stress occurring in Parkinson's disease appear not be related to the administration of L-DOPA. Some alterations of oxidative stress are found in other basal ganglia in degenerative disorders (multiple system atrophy, progressive supranuclear palsy, Huntington's disease) but these have not been investigated to the same extent. Similarly, examination of biochemical changes occurring in Alzheimer's disease, motor neurone disease and diabetic neuropathy also suggest the involvement of free radical mediated mechanisms as a component of neurodegeneration. It is probable that irrespective of the primary cause of individual neurodegenerative disorder, the onset of oxidative stress is a common mechanism by which neuronal death occurs and which contributes to disease progression. Clearly, therapeutic strategies aimed at limiting free radical production and oxidative stress and/or damage may slow the advance of neurodegenerative disease.
Jenner
P
P
Biomedical Sciences Division, King's College London, UK.
D000544:Alzheimer Disease / Q000378:metabolism*; D001480:Basal Ganglia Diseases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000627:therapeutic use*; D015259:Dopamine Agents / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*
D015259:Dopamine Agents; D004295:Dihydroxyphenylalanine; D005978:Glutathione