Oxidative stress and mitochondrial dysfunction in neurodegeneration.
In the last 4 years much progress has been made in the understanding of mitochondrial disorders. Point-mutations, deletions and depletion of the mitochondrial genome are associated with disorders like Leber's disease, MERRF (Myoclonus Epilepsia with Ragged Red Fibers), MELAS (mitochondrial Myopathy, Encephalopathy, Lactic acidosis and Stroke-like episodes) and several others. Recently, mitochondrial dysfunctions have been also related to neurodegenerative disorders like Parkinson's disease and to aging. Since the brain depends mostly on mitochondrial energy supply, mitochondrial dysfunctions may affect the nervous system more severely than other tissues causing or worsening diseases and playing a role in the biological deterioration of aging. Furthermore, the mitochondrial energy supply is associated with the production of highly reactive oxygen species. Ninety-five percent of the molecular oxygen is metabolized within the mitochondria by the electron-transport chain so that mitochondria are highly exposed to oxidative stress which may damage selected neuronal populations. Oxygen radicals created during respiration induce mitochondrial dysfunction which accelerates the production of more deleterious species of oxygen. The latter step further increases mitochondrial malfunction, thus intensifying and perpetuating the cycle. These two mechanisms combined may lead to cell death in brain and other tissues with high metabolic rate. Therefore, in neurodegenerative disorders such as Parkinson's disease mitochondrial dysfunction and oxidative stress may cause or worsen the clinical features.
Tritschler
H J
HJ
Medical Research Departement, Asta Medica, Frankfurt-am-Main, Germany.
Packer
L
L
Medori
R
R
D000975:Antioxidants / Q000494:pharmacology; D002490:Central Nervous System / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D008670:Metals / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009410:Nerve Degeneration / Q000235:genetics / Q000502:physiology*; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D018384:Oxidative Stress / Q000235:genetics*; D010101:Oxygen Consumption; D017354:Point Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D004272:DNA, Mitochondrial; D008670:Metals; D017382:Reactive Oxygen Species