Bioenergetic approaches for neuroprotection in Parkinson's disease.
There is considerable evidence suggesting that mitochondrial dysfunction and oxidative damage may play a role in the pathogenesis of Parkinson's disease (PD). This possibility has been strengthened by recent studies in animal models, which have shown that a selective inhibitor of complex I of the electron transport gene can produce an animal model that closely mimics both the biochemical and histopathological findings of PD. Several agents are available that can modulate cellular energy metabolism and that may exert antioxidative effects. There is substantial evidence that mitochondria are a major source of free radicals within the cell. These appear to be produced at both the iron-sulfur clusters of complex I as well as the ubiquinone site. Agents that have shown to be beneficial in animal models of PD include creatine, coenzyme Q(10), Ginkgo biloba, nicotinamide, and acetyl-L-carnitine. Creatine has been shown to be effective in several animal models of neurodegenerative diseases and currently is being evaluated in early stage trials in PD. Similarly, coenzyme Q(10) is also effective in animal models and has shown promising effects both in clinical trials of PD as well as in clinical trials in Huntington's disease and Friedreich's ataxia. Many other agents show good human tolerability. These agents therefore are promising candidates for further study as neuroprotective agents in PD.
Beal
M Flint
MF
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA. fbeal@mail.med.cornell.edu
D000108:Acetylcarnitine / Q000494:pharmacology* / Q000627:therapeutic use*; D003067:Coenzymes; D003401:Creatine / Q000494:pharmacology* / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects*; D005609:Free Radicals / Q000378:metabolism; D020441:Ginkgo biloba; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D009536:Niacinamide / Q000494:pharmacology* / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*
D003067:Coenzymes; D005609:Free Radicals; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D014451:Ubiquinone; D009536:Niacinamide; D000108:Acetylcarnitine; D008063:Thioctic Acid; C024989:coenzyme Q10; D003401:Creatine