2. Academic Validation
  3. CHCHD2 up-regulation in Huntington disease mediates a compensatory protective response against oxidative stress

CHCHD2 up-regulation in Huntington disease mediates a compensatory protective response against oxidative stress

  • Cell Death Dis. 2024 Feb 10;15(2):126. doi: 10.1038/s41419-024-06523-x.
Xuanzhuo Liu # 1 2 3,  Fang Wang # 1 2,  Xinman Fan # 1 2,  Mingyi Chen 1 2,  Xiaoxin Xu 1 2,  Qiuhong Xu 4,  Huili Zhu 1,  Anding Xu 1 2,  Mahmoud A Pouladi 5,  Xiaohong Xu 6 7
Affiliations

Affiliations

  • 1 Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, 613 Huangpu Avenue West, Guangzhou, Guangdong, 510632, China.
  • 2 Clinical Neuroscience Institute, Jinan University, 613 Huangpu Avenue West, Guangzhou, Guangdong, 510632, China.
  • 3 Department of Neurology, Taihe Hospital of Shiyan, Affiliated Hospital of Hubei Medical University, Shiyan, 442000, China.
  • 4 Department of Plastic Surgery, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue West, Guangzhou, Guangdong, 510632, China.
  • 5 Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Djavad Mowafaghian Centre for Brain Health, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, V5Z 4H4, Canada. mahmoud.pouladi@ubc.ca.
  • 6 Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, 613 Huangpu Avenue West, Guangzhou, Guangdong, 510632, China. xiaohongxu86@jnu.edu.cn.
  • 7 Clinical Neuroscience Institute, Jinan University, 613 Huangpu Avenue West, Guangzhou, Guangdong, 510632, China. xiaohongxu86@jnu.edu.cn.
  • # Contributed equally.
PMID: 38341417 DOI: 10.1038/s41419-024-06523-x
Abstract

Huntington disease (HD) is a neurodegenerative disease caused by the abnormal expansion of a polyglutamine tract resulting from a mutation in the HTT gene. Oxidative stress has been identified as a significant contributing factor to the development of HD and Other neurodegenerative diseases, and targeting anti-oxidative stress has emerged as a potential therapeutic approach. CHCHD2 is a mitochondria-related protein involved in regulating cell migration, anti-oxidative stress, and anti-apoptosis. Although CHCHD2 is highly expressed in HD cells, its specific role in the pathogenesis of HD remains uncertain. We postulate that the up-regulation of CHCHD2 in HD models represents a compensatory protective response against mitochondrial dysfunction and oxidative stress associated with HD. To investigate this hypothesis, we employed HD mouse striatal cells and human induced pluripotent stem cells (hiPSCs) as models to examine the effects of CHCHD2 overexpression (CHCHD2-OE) or knockdown (CHCHD2-KD) on the HD phenotype. Our findings demonstrate that CHCHD2 is crucial for maintaining cell survival in both HD mouse striatal cells and hiPSCs-derived neurons. Our study demonstrates that CHCHD2 up-regulation in HD serves as a compensatory protective response against oxidative stress, suggesting a potential anti-oxidative strategy for the treatment of HD.

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