Central nicotinic receptors, neurotrophic factors and neuroprotection

The multiple combinations of nAChR subunits identified in central nervous s tructures posses distinct pharmacological and physiological properties. A g rowing number of data have shown that compounds interacting with neuronal n AChRs have, both in vivo and in vitro, the potential to be neuroprotective and that treatment with nAChR agonists elicit long-lasting improving of cog nitive performance in a variety of behavioural tests in rats, monkeys and h umans. Epidemiological and clinical studies suggested also a potential neur oprotective/trophic role of (-)-nicotine in neurodegenerative disease, such as Alzheimer's and Parkinson's disease. Taken together experimental and cl inical data largely indicate a neuroprotective/trophic role of nAChR activa tion involving mainly alpha 7 and alpha 4 beta 2 nAChR subtypes, as evidenc ed using selective nAChR antagonists, and by potent nAChR agonists recently found displaying efficacy and/or larger selective affinities than (-)-nico tine for neuronal nAChR subtypes. A neurotrophic factor gene regulation by nAChR signalling has been taken into consideration as possible mechanism in volved in neuroprotective/trophic effects by nAChR activation and has evide nced an involvement of the fibroblast growth factor (FGF-2) gene as a targe t of nAChR signalling. These findings suggested that FGF-2 could be involve d, according to the FGF-2 neurotrophic functions, in nAChR mechanisms media ting the neuronal survival, trophism and plasticity. (C) 2000 Elsevier Scie nce B.V. All rights reserved.