Glutaredoxin-1 attenuates transactive response DNA-binding protein 43–induced neurotoxicity by suppressing oxidative stress and transactive response DNA-binding protein 43 aggregation
Year: 2026
Type: article
Abstract: OBJECTIVE: Cytoplasmic aggregation of transactive response DNA-binding protein 43 (TDP-43) represents pathological hallmarks of TDP-43 proteinopathies. Accumulating evidence indicates that oxidative stress plays a pivotal role in these disorders by promoting TDP-43 aggregation and subsequent neurotoxicity. Glutaredoxin-1 (Grx1) is a key antioxidant enzyme that maintains cellular redox homeostasis. In this study, we investigated the role of Grx1 in TDP-43 proteinopathy. METHODS: We examined the effects of Grx1 in neuro-2a cells expressing human wild-type TDP-43 (N2a-hTDP-43), a cellular model of TDP-43 proteinopathy characterized by increased oxidative stress, TDP-43 aggregation, and neurotoxicity. RESULTS: In N2a-hTDP-43 cells, Grx1 expression was increased in parallel with elevated oxidative stress. Increasing Grx1 significantly suppresses intracellular oxidative stress and cytoplasmic TDP-43 aggregation in N2a-hTDP-43 cells. Notably, increasing Grx1 significantly reduces cleaved caspase-3 levels in N2a-hTDP-43 cells, indicating reduced neurotoxicity. CONCLUSION: Collectively, our findings demonstrate that Grx1 attenuates neurotoxicity by suppressing oxidative stress and TDP-43 aggregation, highlighting its potential as a therapeutic target for TDP-43 proteinopathies.
Source: Neuroreport
Institutions: Kyungpook National University, Korea Brain Research Institute
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7155190549