α7 nicotinic acetylcholine receptor mediated neuroprotection in Parkinson's disease

Parkinson's disease (PD) is characterized by relatively selective degeneration of dopaminergic neurons in the substantia nigra and loss of dopamine in the striatum. More than 50 epidemiological studies confirmed the low incidence of PD in smokers. Examining the distribution of subtypes of nicotinic acetylcholine receptors (nAChRs) in dopaminergic neurons of nigrostriatal system and its change in PD patients is quite important to elucidate possible neuroprotective cascade triggered by nicotine. Evidences of nAChR-mediated protection against neurotoxicity induced by rotenone, 6- hydroxydopamine (6-OHDA), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are briefly reviewed. In rotenone- and 6-OHDA-induced PD models, nAChR-mediated neuroprotection was blocked not only by α4β2 but also by α7 nAChR antagonists. The survival signal transduction, α7 nAChR-Src family-PI3K-Akt/PKB cascade and subsequent upregulation of Bcl-2, would lead to neuroprotection. These findings suggest that nAChR-mediated neuroprotection is achieved through subtypes of nAChRs and common signal cascades. An early diagnosis and protective therapy with specific nAChR modulations could be effective in delaying the progression of PD.