Activation of α7-nAChRs Promotes the Clearance of α-Synuclein and Protects Against Apoptotic Cell Death Induced by Exogenous α-Synuclein Fibrils.

摘要: Misfolding and abnormal aggregation of α-synuclein (αSyn) have been shown to increase the risk developing Parkinson's disease (PD). Finding some way reduce αSyn is particularly important for treatment PD. The main route in prion-like spreading cholinergic innervated vagus nervous system central neurons. Since degenerative changes death neurons also run through pathological process PD, we hypothesize an involvement aggregation. α7 nicotinic acetylcholine receptors (α7-nAChRs) are one most abundant nAChRs mammalian brain. Using nicotine a selective α7-nAChRs agonist PNU-282987, found protective effect on cell damage induced by αSyn-PFF (preformed fibrils) inhibiting apoptotic death. We further discovered additive clearance normal stably transduced SH-SY5Y cells. Moreover, using knockout mice, noticed that deficiency increased deposition aggravated loss dopaminergic chronic MPTP mouse model Our findings first time indicated activation exhibited neuroprotective pathology promoting αSyn.