In:
Brain Pathology, Wiley, Vol. 26, No. 2 ( 2016-03), p. 167-176
Abstract:
P arkinson's disease ( PD ) is the most prevalent movement disorder characterized by selective loss of midbrain dopaminergic ( DA ) neurons. MicroRNA ‐124 (mi R ‐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 mi R ‐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 mi R ‐124. In addition, we identified a target of mi R ‐124, B im that mediated the neuroprotection of mi R ‐124. Indeed, treatment of mi R ‐124 agomir in MPTP ‐treated mice inhibited B im expression, thus suppressing B ax 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 mi R ‐124 could regulate apoptosis and impaired autophagy process in the MPTP model of PD , thus reducing the loss of DA neurons.
Type of Medium:
Online Resource
ISSN:
1015-6305
,
1750-3639
DOI:
10.1111/bpa.2016.26.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2029927-8
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