MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson's Disease by Targeting to Bim.
Brain Pathol
; 26(2): 167-76, 2016 Mar.
Article
en En
| MEDLINE
| ID: mdl-25976060
ABSTRACT
Parkinson's disease (PD) is the most prevalent movement disorder characterized by selective loss of midbrain dopaminergic (DA) neurons. MicroRNA-124 (miR-124) is abundantly expressed in the DA neurons and its expression level decreases in the 1-methyl-4-pheny-1, 2, 3, 6-tetrahydropyridine (MPTP) model of PD. However, whether the upregulation of miR-124 could attenuate neurodegeneration remains unknown. Here, we employed miR-124 agomir and miR-124 mimics to upregulate miR-124 expression in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y cells, respectively. We found that loss of DA neurons and striatal dopamine in MPTP-treated mice was significantly reduced by upregulating miR-124. In addition, we identified a target of miR-124, Bim that mediated the neuroprotection of miR-124. Indeed, treatment of miR-124 agomir in MPTP-treated mice inhibited Bim expression, thus suppressing Bax translocation to mitochondria. Moreover, impaired autophagy process in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y cells characterized as autophagosomes (AP) accumulation and lysosomal depletion were alleviated by the upregulation of miR-124. Taken together, these results indicate that upregulation of miR-124 could regulate apoptosis and impaired autophagy process in the MPTP model of PD, thus reducing the loss of DA neurons.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Intoxicación por MPTP
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MicroARNs
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Proteína 11 Similar a Bcl2
Idioma:
En
Revista:
Brain Pathol
Asunto de la revista:
CEREBRO
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PATOLOGIA
Año:
2016
Tipo del documento:
Article