Neurotrophic effects of central nicotinic receptor activation.
A growing number of data have shown that compounds interacting with neuronal nicotinic acetylcholine receptors (nAChRs) have, both in vivo and in vitro, the potential to be neuroprotective and that treatment with nAChR agonists elicit long-lasting improvement of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Epidemiological and clinical studies suggested also a potential neuroprotective/trophic role of (-)-nicotine in neurodegenerative disease, such as Alzheimer's disease and Parkinson's disease. This neuroprotective/trophic role of nAChR activation has been mainly mediated by alpha7 and alpha4beta2 nAChR subtypes, as evidenced using selective nAChR antagonists, and by potent nAChR agonists recently found displaying efficacy and/or larger selective affinities than (-)-nicotine for neuronal nAChR subtypes. A neurotrophic factor gene regulation by nAChR signalling has been taken into consideration as a possible mechanism involved in neuroprotective/trophic effects of nAChR activation and has given evidence that the fibroblast growth factor (FGF-2) gene is a target for nAChR signalling. These findings suggested that FGF-2 could be involved, in view of its neurotrophic functions, in nAChR mechanisms mediating neuronal survival, trophism and plasticity.
Belluardo
N
N
Institute of Human Physiology, University of Palermo, Italy. Belluard@mbox.unict.it
Mudo
G
G
Blum
M
M
Amato
G
G
Fuxe
K
K
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D016222:Fibroblast Growth Factor 2