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 nigrapars 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 andMPTP-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.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Wang M,Wan C,He T,Han C,Zhu K,Waddington JL,Zhen Xdoi
10.1016/j.neuropharm.2020.108360subject
Has Abstractpub_date
2020-10-26 00:00:00pages
108360eissn
0028-3908issn
1873-7064pii
S0028-3908(20)30428-7pub_type
杂志文章abstract：:We evaluated the anticonvulsant efficacy of the antiepileptic drugs (AEDs) lamotrigine (LTG) and felbamate (FBM) in amygdala kindled rats that had been preselected with respect to their response to phenytoin. Anticonvulsant response was tested by determining the afterdischarge threshold (ADT), i.e., a sensitive measur...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00039-3
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abstract：:Recent genetic and pharmacological studies have implicated the α3, β4 and α5 subunits of the nicotinic acetylcholine receptor (nAChR) in dependence to nicotine and other abused drugs and nicotine withdrawal. The α3β4* nAChR subtype has been shown to co-assemble with the α5 or β3 nAChR subunits, and is found mainly in ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.09.023
更新日期：2014-02-01 00:00:00
abstract：:Marijuana smoking is recognised to impair human cognition and learning, but the mechanisms by which this occurs are not well characterised. This article focuses exclusively on the hippocampus to review the effects of cannabinoids on hippocampal function and evaluate the evidence that hippocampal cannabinoid receptors ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0028-3908(02)00060-6
更新日期：2002-06-01 00:00:00
abstract：:N-Methyl-D-aspartate (NMDA) receptors are important CNS target sites of alcohols, but the site and mechanism of action of alcohols on NMDA receptors remains unclear. In CHO-K1 cells transfected with NR1/NR2B NMDA receptor subunits, ethanol inhibited NMDA-activated current with an IC(50) of 138 mM. Truncation of the in...
journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2004.08.021
更新日期：2004-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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更新日期：1992-03-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.06.023
更新日期：2008-01-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.02.003
更新日期：2015-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.01.021
更新日期：2018-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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更新日期：2012-02-01 00:00:00
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2001-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：1984-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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abstract：:The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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更新日期：2010-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90012-0
更新日期：1982-07-01 00:00:00
abstract：:The present study was designed to clarify whether α2-adrenoceptors of the basolateral amygdala (BLA) are involved in nicotine-induced anxiogenic-like behaviours. Adult male Wistar rats were bilaterally cannulated in the BLA and anxiety-like behaviours were assessed in an elevated plus maze (EPM) task. Systemic intrape...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.02.010
更新日期：2016-06-01 00:00:00
