4.7 Article

miR-196a provides antioxidative neuroprotection via USP15/Nrf2 regulation in Huntington's disease

期刊

FREE RADICAL BIOLOGY AND MEDICINE
卷 209, 期 -, 页码 292-300

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2023.10.407

关键词

miR-196a; Antioxidative effect; Nrf2; USP15; Reactive oxygen species; Huntington's disease

向作者/读者索取更多资源

This study reveals the multifaceted role of miR-196a in Huntington's disease, including reducing reactive oxygen species levels and cell death through antioxidative effects, enhancing the transcription of antioxidant genes via the nuclear factor erythroid 2 pathway, and counteracting mutant Huntingtin protein aggregation through targeting ubiquitin-specific peptidase 15. These findings highlight the potential of miR-196a as a therapeutic avenue for ameliorating oxidative stress and neurodegeneration in Huntington's disease.
Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by the accumulation of mutant Huntingtin protein (mHTT) and oxidative stress-induced neuronal damage. Based on previous reports, microRNA-196a (miR-196a) has emerged as a potential therapeutic target due to its neuroprotective effects in various neurodegenerative diseases. However, whether miR-196a functions through antioxidative effects is still unknown. In this study, we demonstrated that HD models, both in vitro and in vivo, exhibit elevated levels of reactive oxygen species (ROS) and increased neuronal death, and miR-196a mitigates ROS levels and reduces cell death in HD cells. Moreover, we elucidated that miR-196a facilitates the translocation of nuclear factor erythroid 2 (Nrf2) into the nucleus, enhancing the transcription of antioxidant genes, including heme oxygenase-1 (HO-1). We further identified ubiquitin-specific peptidase 15 (USP15), a direct target of miR-196a related to the Nrf2 pathway, and USP15 exacerbates mHTT aggregate formation while partially counteracting miR-196a-induced reductions in mHTT levels. Taken together, these findings shed light on the multifaceted role of miR-196a in HD, highlighting its potential as a therapeutic avenue for ameliorating oxidative stress and neurodegeneration in this debilitating disease.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据