Sigma-1 receptor regulates mitophagy in dopaminergic neurons and contributes to dopaminergic protection.
1-Methyl-4-phenylpyridinium
/ toxicity
Animals
Autophagy-Related Protein-1 Homolog
/ drug effects
Cell Line
Dopaminergic Neurons
/ drug effects
Gene Knockdown Techniques
Mice
Mitochondria
/ drug effects
Mitophagy
/ drug effects
Morpholines
/ pharmacology
Parkinsonian Disorders
/ genetics
Pars Compacta
/ drug effects
Phenazocine
/ analogs & derivatives
Phosphorylation
Protein Kinases
/ drug effects
Protein Serine-Threonine Kinases
/ drug effects
Protein Stability
/ drug effects
Protein Transport
/ drug effects
Receptors, sigma
/ agonists
Signal Transduction
Substantia Nigra
/ drug effects
Ubiquitin
/ drug effects
Ubiquitin-Protein Ligases
/ drug effects
Sigma-1 Receptor
Mitophagy
PD
PINK1/Parkin
PRE-084
Sigma-1 receptor
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
15 09 2021
15 09 2021
Historique:
received:
24
05
2020
revised:
12
10
2020
accepted:
16
10
2020
pubmed:
31
10
2020
medline:
3
2
2022
entrez:
30
10
2020
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 33122030
pii: S0028-3908(20)30428-7
doi: 10.1016/j.neuropharm.2020.108360
pii:
doi:
Substances chimiques
Morpholines
0
Receptors, sigma
0
Ubiquitin
0
2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
138847-85-5
SK&F 10047
7619-35-4
Ubiquitin-Protein Ligases
EC 2.3.2.27
parkin protein
EC 2.3.2.27
Protein Kinases
EC 2.7.-
Tbk1 protein, mouse
EC 2.7.1.-
Autophagy-Related Protein-1 Homolog
EC 2.7.11.1
PTEN-induced putative kinase
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Ulk1 protein, mouse
EC 2.7.11.1
Phenazocine
J0ND6N0AQC
1-Methyl-4-phenylpyridinium
R865A5OY8J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108360Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.