Neuroprotective therapy for Parkinson's disease.
The concept of neuroprotection relates to the fact that intervention may be able to interfere with the pathogenesis of neuronal cell death. Neuroprotective therapy may make it possible to delay disease progression or prevent the disease altogether. The pathophysiological mechanism of cell death in Parkinson's disease is unknown; however, hypotheses have been developed. The discovery that the toxin MPTP can cause Parkinson's disease both in humans and in animals strengthened the hypothesis that either exogenous or endogenous toxins may be involved in the mechanism of cell death in Parkinson's disease. The mechanism of MPTP toxicity has been elucidated, lending several possible mechanisms for therapeutic intervention in Parkinson's disease. Current data suggest that oxidative stress may play a prominent role in the pathogenesis of Parkinson's disease. It is possible that the generation of free radicals leads to neuronal cell death. There is also evidence that mitochondrial damage may play a role in the pathogenesis of Parkinson's disease. Other theories of possible pathogenesis include excitotoxicity, disturbances of calcium homeostasis, immunological mechanisms, and infectious etiologies. The first agent to be tested as a candidate for neuroprotection was the MAO-B inhibitor deprenyl. Evidence is reviewed for and against the theory that this drug is neuroprotective.
Koller
W C
WC
Department of Neurology, University of Kansas Medical Center, Kansas City 66160-7314, USA.
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D006801:Humans; D007239:Infections / Q000150:complications; D020267:MPTP Poisoning; D008928:Mitochondria / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D012642:Selegiline / Q000627:therapeutic use
D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D012642:Selegiline