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Super-enhancer-driven Sorting Nexin 5 expression promotes dopaminergic neuronal ferroptosis in Parkinson's disease models.
Si, Wenwen; Huang, Zifeng; Li, Xinrong; Zhao, Lijun; Ji, Yichun; Li, Hang; Liu, Xuelei; Ye, Shanyu; Chen, Dongfeng; Liu, Helu; Kuang, Weihong; Zhu, Meiling.
Afiliação
  • Si W; Shenzhen Bao'an Traditional Chinese Medicine Hospital (Group), Shenzhen, China.
  • Huang Z; Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
  • Li X; Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
  • Zhao L; Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
  • Ji Y; Shenzhen Bao'an Traditional Chinese Medicine Hospital (Group), Shenzhen, China.
  • Li H; Shenzhen Bao'an Traditional Chinese Medicine Hospital (Group), Shenzhen, China.
  • Liu X; Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
  • Ye S; Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Chen D; Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Liu H; Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
  • Kuang W; The Second Clinical Medical College, Guangdong Medical University, Dongguan, China. Electronic address: kuangwh@gdmu.edu.cn.
  • Zhu M; Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China. Electronic address: meilingzhu2020@126.com.
Biochem Biophys Res Commun ; 567: 35-41, 2021 08 27.
Article em En | MEDLINE | ID: mdl-34134000
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide. Recent studies revealed that the ferroptosis pathway is involved in the death process of dopaminergic neurons in PD. The aberrant endosomal sorting pathway, which results in aberrant iron level in eukaryotic cells, may serve a role in the ferroptosis pathway in PD condition. However, its specific molecular mechanisms remained unclear. In the present study, we performed chromatin immunoprecipitation (ChIP) assay, the rank ordering of super-enhancers (ROSE) algorithm, and RNA interference (RNAi) to explore the regulatory mechanism of PD-specific super-enhancer (SE) in the endosomal sorting pathway and ferroptosis pathway of 6-OHDA-lesioned rats and cells. The ChIP assay and ROSE algorithm results showed that there are specific SEs expression in 6-OHDA-lesioned SNc of PD rats, and the most significant expression gene is Sorting Nexin 5 (SNX5). SNX5 silencing by RNAi experiments significantly decreased the level of ferroptosis in 6-OHDA-lesioned PC12 cells, suggesting the correlation between the SNX5, ferroptosis, and PD. In conclusion, this study investigated the mechanism by which PD-specific SE driven SNX5 promoted the ferroptosis level in PD models. This study further improved the understanding of the mechanism of ferroptosis during PD injury and provided potential therapeutic targets and clinical diagnostic markers in PD condition.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Nexinas de Classificação / Neurônios Dopaminérgicos / Ferroptose Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Nexinas de Classificação / Neurônios Dopaminérgicos / Ferroptose Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article