CRISPR/Cas۹-mediated knockout of NEAT۱ attenuates neurotoxicity in ۶-hydroxydopamine model of Parkinson’s disease

Objective(s): Parkinson’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 Methods: This study explores the role of the long non-coding RNA NEAT۱ in PD by employing CRISPR/Cas۹-mediated knockout in SH-SY۵Y neuroblastoma cells treated with ۶-hydroxydopamine (۶-OHDA).Results: Deletion of NEAT۱ 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, NEAT۱ knockout was accompanied by increased hsa-let-۷a-۵p and decreased miR-۵۰۶-۳p expression, suggesting its function as a competing endogenous RNA (ceRNA) in miRNA-mediated stress pathways. Tyrosine hydroxylase (TH) levels remained unchanged, indicating that NEAT۱ may influence neurotoxicity through post-transcriptional mechanisms.Conclusion: These results suggest NEAT۱ 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 NEAT۱’s dualistic roles in neurodegeneration and underscore its potential as a therapeutic target in PD.

کلیدواژه ها:

Alpha-synuclein ، Apoptosis ، CRISPR/Cas۹ ، Long non-coding RNA ، microRNAs ، NEAT۱ ، Oxidative stress ، Parkinson’s disease