Effects of 7 nicotinic acetylcholine receptor agonist against -synuclein-induced neurotoxicity

The alpha 7 neuronal nicotinic acetylcholine receptor (alpha 7 nAChR) is a potential target for the development of Parkinson's disease (PD) therapeutics. alpha-Synuclein (alpha-Syn), a principal component of Lewy bodies (cytoplasmic inclusions), is a major contributor to PD pathophysiology. Previous studies have demonstrated that activating alpha 7 nAChR protects against nigrostriatal dopamine degeneration in acute and chronic PD animal models induced by 6-hydroxydopamine and rotenone, respectively. In the present study, we investigated the effects of PNU282987, a selective alpha 7 nAChR agonist, against alpha-Syn-induced neurotoxicity in alpha-Syn(WT)-, alpha-Syn(A30P)-, and alpha-Syn(E46K)-N2a cells. PNU282987 exhibited substantial neuroprotection against both wild-type and mutant-type alpha-Syn-induced toxicity. Furthermore, PNU282987 promoted transcription factor EB activity and reduced intracellular alpha-Syn protein levels through autophagy induction. These results highlight the therapeutic potential of alpha 7 nAChR activation in diseases characterized by alpha-Syn aggregation, such as PD.