CRISPR/Cas9-mediated knockout of NEAT1 attenuates neurotoxicity in 6-hydroxydopamine model of Parkinson’s disease

Articles in Press

Document Type : Original Article

Authors

1 Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran

2 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

3 Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

4 Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman, Iran

5 Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

6 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

7 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

8 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

9 Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran

10 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman, Iran

10.22038/ijbms.2026.93063.20075

Abstract

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 NEAT1 in PD by employing CRISPR/Cas9-mediated knockout in SH-SY5Y neuroblastoma cells treated with 6-hydroxydopamine (6-OHDA).
Results: Deletion 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.
Conclusion: These 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.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 06 May 2026

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