| First Author | Zhao J | Year | 2021 |
| Journal | Front Cell Dev Biol | Volume | 9 |
| Pages | 637319 | PubMed ID | 33718373 |
| Mgi Jnum | J:336945 | Mgi Id | MGI:6807199 |
| Doi | 10.3389/fcell.2021.637319 | Citation | Zhao J, et al. (2021) Activation of alpha7-nAChRs Promotes the Clearance of alpha-Synuclein and Protects Against Apoptotic Cell Death Induced by Exogenous alpha-Synuclein Fibrils. Front Cell Dev Biol 9:637319 |
| abstractText | Misfolding and abnormal aggregation of alpha-synuclein (alphaSyn) have been shown to increase the risk of developing Parkinson's disease (PD). Finding some way to reduce the aggregation of alphaSyn is particularly important for the treatment of PD. The main route in prion-like alphaSyn spreading is the cholinergic innervated vagus nervous system and central cholinergic neurons. Since the degenerative changes and death of cholinergic neurons also run through the pathological process of PD, we hypothesize an involvement of the cholinergic system in alphaSyn aggregation. The alpha7 nicotinic acetylcholine receptors (alpha7-nAChRs) are one of the most abundant nAChRs in the mammalian brain. Using nicotine and a selective alpha7-nAChRs agonist PNU-282987, we found a protective effect of alpha7-nAChRs on the cell damage induced by alphaSyn-PFF (preformed fibrils) through inhibiting apoptotic cell death. We further discovered an additive effect of alpha7-nAChRs on the clearance of alphaSyn in normal and alphaSyn stably transduced SH-SY5Y cells. Moreover, using alpha7-nAChRs knockout mice, we noticed that alpha7-nAChRs deficiency increased the deposition of alphaSyn and aggravated the loss of dopaminergic neurons in a chronic MPTP mouse model of PD. Our findings for the first time indicated that alpha7-nAChRs activation exhibited a neuroprotective effect on alphaSyn pathology and aggregation by promoting the clearance of alphaSyn. |
