Neuroprotective Role of E3 Ubiquitin Ligase TRIM2 in Parkinson's Disease: Attenuation of Oxidative Stress and Apoptosis via Promoting ELAVL1 Ubiquitination.

Overview

1. Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2. Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Abstract

Background: Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, where oxidative stress and neuronal apoptosis are key pathogenic events. In this study, we identified a downregulated TRIM2 in the substantia nigra pars compacta (SNc) of PD rats based on label‐free proteomics. However, the impact of TRIM2 on PD is unknown.

Methods: We used 6‐hydroxydopamine (6‐OHDA) to construct a PD model in vivo and in vitro.

Results: TRIM2 overexpression alleviated neurobehavioral deficits, mitigated the loss of dopaminergic neurons, and suppressed oxidative stress and apoptosis in the SNc of PD rats. These effects were also observed in the 6‐OHDA‐treated differentiated BE (2)‐M17 cells. Mechanistically, the RNA‐binding protein ELAVL1 was identified as a critical downstream target, given that the database predicts it to be a TRIM2‐interacted protein and a PD‐related protein. Herein, TRIM2 directly interacted with ELAVL1 and promoted its ubiquitin‐mediated degradation. Crucially, rescue experiments confirmed that the neuroprotection conferred by TRIM2 was counteracted by ELAVL1 overexpression in the 6‐OHDA‐treated BE (2)‐M17 cells that exhibited neuronal‐like properties.

Conclusion: Our findings uncovered a novel TRIM2‐ELAVL1 axis as a pivotal regulatory mechanism in PD pathogenesis, positioning TRIM2 as a potential target for therapeutic intervention in PD.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE7621 — at NCBI GEO; found in the text, “Downregulated TRIM2 Was Identified in the SNc…”

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 4 keywords, 13 MeSH terms, 1 funder, 56 references.

Cite

This paper

Liang, W., Sun, W., Zhao, Z., Song, K., & Jia, J. (2026). Neuroprotective Role of E3 Ubiquitin Ligase TRIM2 in Parkinson's Disease: Attenuation of Oxidative Stress and Apoptosis via Promoting ELAVL1 Ubiquitination. CNS neuroscience & therapeutics, 32(8), e71075. https://doi.org/10.1002/cns.71075

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