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

Siew Chin Chan, Chih Wei Tung, Chia Wei Lin, Yun Shiuan Tung, Po Min Wu, Pei Hsun Cheng, Chuan Mu Chen, Shang Hsun Yang

研究成果: Article同行評審


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.

頁(從 - 到)292-300
期刊Free Radical Biology and Medicine
出版狀態Published - 2023 11月 20

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 生理學(醫學)


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