CRISPR/Cas9-mediated knockout of NEAT1 attenuates neurotoxicity in 6-hydroxydopamine model of Parkinson's disease.
CRISPR/Cas9-mediated knockout of NEAT1 attenuates neurotoxicity in 6-hydroxydopamine model of Parkinson's disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Kerman, IR · Author affiliation
Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran.Location evidence
Guangzhou, CN · Author affiliation
Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, The State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.Location evidence
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Original abstract
ObjectivesParkinson's disease (PD), a progressive neurodegenerative condition, involves the degeneration of dopaminergic neurons and the aggregation of α-synuclein (SNCA); however, the molecular mechanisms of this disorder remain incompletely understood.Materials and methodsThis study explores the role of the long non-coding RNA NEAT1 in PD by employing CRISPR/Cas9-mediated knockout in SH-SY5Y neuroblastoma cells treated with 6-hydroxydopamine (6-OHDA).ResultsDeletion of NEAT1 was associated with increased cellular viability, attenuated both cytotoxicity and apoptosis, and elevated total antioxidant capacity (TAC), alongside a marked down-regulation of SNCA expression. Mechanistically, NEAT1 knockout was accompanied by increased hsa-let-7a-5p and decreased miR-506-3p expression, suggesting its function as a competing endogenous RNA (ceRNA) in miRNA-mediated stress pathways. Tyrosine hydroxylase (TH) levels remained unchanged, indicating that NEAT1 may influence neurotoxicity through post-transcriptional mechanisms.ConclusionThese results suggest NEAT1 is a crucial modulator of neurotoxicity in PD, with its inhibition offering therapeutic promise. Despite the in vitro nature of this study, our findings provide foundational insight into NEAT1's dualistic roles in neurodegeneration and underscore its potential as a therapeutic target in PD.