Central nicotinic receptors, neurotrophic factors and neuroprotection.
The multiple combinations of nAChR subunits identified in central nervous structures possess distinct pharmacological and physiological properties. A growing number of data have shown that compounds interacting with neuronal nAChRs have, both in vivo and in vitro, the potential to be neuroprotective and that treatment with nAChR agonists elicit long-lasting improving 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 and Parkinson's disease. Taken together experimental and clinical data largely indicate a neuroprotective/trophic role of nAChR activation involving mainly 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 possible mechanism involved in neuroprotective/trophic effects by nAChR activation and has evidenced an involvement of the fibroblast growth factor (FGF-2) gene as a target of nAChR signalling. These findings suggested that FGF-2 could be involved, according to the FGF-2 neurotrophic functions, in nAChR mechanisms mediating the neuronal survival, trophism and plasticity.
Belluardo
N
N
Institute of Human Physiology, University of Palermo, Italy. belluard@mbox.unict.it
Mudò
G
G
Blum
M
M
Fuxe
K
K
D000818:Animals; D001921:Brain / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D000882:Haplorhini; D006801:Humans; D009414:Nerve Growth Factors / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011978:Receptors, Nicotinic; D016222:Fibroblast Growth Factor 2