Neuroprotection in Parkinson's disease: an elusive goal.
Parkinson's disease is a chronic progressive condition that causes disability and reduction of quality of life. Symptomatic treatments are effective in the early disease; however, with time, most patients develop motor complications. Neuroprotective therapies are those that can slow disease progression; unfortunately, these agents are not available. Advances in the knowledge of the possible pathogenic events that can lead to nigral cell death have increased dramatically. These mechanisms include oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, alterations in protein degradation, and ultimately apoptosis. Based on these laboratory scientific findings, a number of agents have been studied in clinical trials. However, how to assess disease evolution and establish reliable endpoints is still an unresolved issue. The monoamine oxidase inhibitors selegiline and rasagiline have been shown to be neuroprotective in vitro and in animal models, but so far this property was not demonstrated in clinical trials. Other agents have been studied and still others are undergoing clinical investigation. These include antiexcitotoxicity drugs like riluzole, the bioenergetic agent coenzyme Q10, trophic factors, and antiapoptotic drugs. Laboratory and clinical data suggest that dopamine agonists may have a neuroprotective action, but this has yet to be proven. However, as our basic and clinical knowledge on Parkinson's disease increases, it is likely that a neuroprotective drug will be found.
Koller
William C
WC
Department of Neurology, The Mount Sinai Medical Center, One Gustave L. Levy Place, Annenberg 1494/Box 1137, New York, NY 10029-6574, USA. william.koller@mssm.edu
Cersosimo
Maria G
MG
D000818:Animals; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism
D018491:Dopamine Agonists; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents