Mitochondria, oxidative damage, and inflammation in Parkinson's disease.
The pathogenesis of Parkinson's disease (PD) remains obscure, but there is increasing evidence that impairment of mitochondrial function, oxidative damage, and inflammation are contributing factors. The present paper reviews the experimental and clinical evidence implicating these processes in PD. There is substantial evidence that there is a deficiency of complex I activity of the mitochondrial electron transport chain in PD. There is also evidence for increased numbers of activated microglia in both PD postmortem tissue as well as in animal models of PD. Impaired mitochondrial function and activated microglia may both contribute to oxidative damage in PD. A number of therapies targeting inflammation and mitochondrial dysfunction are efficacious in the MPTP model of PD. Of these, coenzyme Q(10) appears to be particularly promising based on the results of a recent phase 2 clinical trial in which it significantly slowed the progression of PD.
Beal
M Flint
MF
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA. fbeal@med.cornell.edu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003067:Coenzymes; D003401:Creatine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005609:Free Radicals / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D003067:Coenzymes; D005609:Free Radicals; D014451:Ubiquinone; C024989:coenzyme Q10; D003401:Creatine