Nicotine as a potential neuroprotective agent for Parkinson's disease.
Converging research efforts suggest that nicotine and other drugs that act at nicotinic acetylcholine receptors (nAChRs) may be beneficial in the management of Parkinson's disease. This idea initially stemmed from the results of epidemiological studies that demonstrated that smoking is associated with a decreased incidence of Parkinson's disease. The subsequent finding that nicotine administration protected against nigrostriatal damage in parkinsonian animal models led to the idea that nicotine in tobacco products may contribute to this apparent protective action. Nicotine most likely exerts its effects by interacting at nAChRs. Accumulating research indicates that multiple subtypes containing nAChRs, including α4β2, α6β2, and/or α7, may be involved. Stimulation of nAChRs initially activates various intracellular transduction pathways primarily via alterations in calcium signaling. Consequent adaptations in immune responsiveness and trophic factors may ultimately mediate nicotine's ability to reduce/halt the neuronal damage that arises in Parkinson's disease. In addition to a potential neuroprotective action, nicotine also has antidepressant properties and improves attention/cognition. Altogether, these findings suggest that nicotine and nAChR drugs represent promising therapeutic agents for the management of Parkinson's disease.
Center for Health Sciences, SRI International, Menlo Park, California, USA. maryka.quik@sri.com
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D000818:Animals; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D018696:Neuroprotective Agents; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000517:prevention & control*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control; D011978:Receptors, Nicotinic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000453:epidemiology; D013378:Substantia Nigra / Q000473:pathology
D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine