MiR-29a efficiently suppresses the generation of reactive oxygen species and α-synuclein in a cellular model of Parkinson's disease by potentially targeting GSK-3ß.
Eur J Pharmacol
; 974: 176615, 2024 Jul 05.
Article
in En
| MEDLINE
| ID: mdl-38685306
ABSTRACT
MicroRNA-29a (miR-29a) has been suggested to serve a potential protective function against Parkinson's disease (PD); however, the exact molecular mechanisms remain elusive. This study explored the protective role of miR-29a in a cellular model of PD using SH-SY5Y cell lines through iTRAQ-based quantitative proteomic and biochemistry analysis. The findings showed that using a miR-29a mimic in SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+) significantly decreased cell death and increased mitochondrial membrane potential. It also reduced mitochondrial reactive oxygen species (ROS) and the production of α-synuclein. Subsequent heatmap analysis using iTRAQ-based quantitative proteomics revealed remarkably contrasting protein expression profiles for 882 genes when comparing the groups treated with miR-29a mimic plus MPP + against the control group treated solely with MPP+. The KEGG pathway analysis of these 882 genes indicated the substantial role of miR-29a in the PD pathway (P = 1.58x10-5) and highlighted its function in mitochondrial genes. Furthermore, treatment with a miR-29a mimic in SH-SY5Y cells reduced the levels of GSK-3ß, phosphorylated GSK-3ß, and cleaved caspase-7 following exposure to MPP+. The miR-29a mimic also upregulated the expressions of α-synuclein clearance proteins FYCO1 and Rab7 in this cellular PD model, thereby inhibiting the production of α-synuclein. Luciferase activity analysis confirmed the specific binding of miR-29a to the 3' untranslated region (3'UTR) of GSK-3ß, leading to its repression. Our findings demonstrated miR-29a's neuroprotective role in mitochondrial function and highlighted its potential to inhibit ROS and α-synuclein production, offering possible therapeutic avenues for PD treatment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parkinson Disease
/
Reactive Oxygen Species
/
MicroRNAs
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Alpha-Synuclein
/
Glycogen Synthase Kinase 3 beta
Limits:
Humans
Language:
En
Journal:
Eur J Pharmacol
/
Eur. j. pharmacol
/
European journal of pharmacology
Year:
2024
Document type:
Article
Affiliation country:
Taiwán
Country of publication:
Países Bajos