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- W3096009901 endingPage "108360" @default.
- W3096009901 startingPage "108360" @default.
- W3096009901 abstract "Mitochondria are essential for neuronal survival and function, and mitochondrial dysfunction plays a critical role in the pathological development of Parkinson's disease (PD). Mitochondrial quality control is known to contribute to the survival of dopaminergic (DA) neurons, with mitophagy being a key regulator of the quality control system. In this study, we show that mitophagy is impaired in the substantia nigra pars compacta (SNc) of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treatment with the sigma-1 receptor (Sig 1R) agonist 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) reduced loss of DA neurons, restored motor ability and MPTP-induced damage to mitophagy activity in the SNc of PD-like mice. Additionally, knockdown of Sig 1R in SH-SY5Y DA cells inhibited mitophagy and enhanced 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity, whereas application of the Sig 1R selective agonist SKF10047 promoted clearance of damaged mitochondria. Moreover, knockdown of Sig 1R in SH-SY5Y cells resulted in decreased levels of p-ULK1 (Unc-51 Like Autophagy Activating Kinase 1) (Ser555), p-TBK1 (TANK Binding Kinase 1) (Ser172), p-ubiquitin (Ub) (Ser65), Parkin recruitment, and stabilization of PTEN-induced putative kinase 1 (PINK1) in mitochondria. The present data provide the first evidence for potential roles of PINK1/Parkin in Sig 1R-modulated mitophagy in DA neurons." @default.
- W3096009901 created "2020-11-09" @default.
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- W3096009901 date "2021-09-01" @default.
- W3096009901 modified "2023-10-12" @default.
- W3096009901 title "Sigma-1 receptor regulates mitophagy in dopaminergic neurons and contributes to dopaminergic protection" @default.
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- W3096009901 doi "https://doi.org/10.1016/j.neuropharm.2020.108360" @default.
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- W3096009901 hasPublicationYear "2021" @default.
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