Your browser doesn't support javascript.
loading
Inhibition of ferroptosis underlies EGCG mediated protection against Parkinson's disease in a Drosophila model.
Xia, Yanzhou; Wang, Hongyan; Xie, Zhongwen; Liu, Zhi-Hua; Wang, Hui-Li.
Afiliación
  • Xia Y; School of Food and Biological Engineering, Hefei University of Technology, No 485 Danxia Road, Hefei, Anhui, 230601, PR China.
  • Wang H; State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, Anhui, PR China.
  • Xie Z; State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, Anhui, PR China.
  • Liu ZH; School of Food and Biological Engineering, Hefei University of Technology, No 485 Danxia Road, Hefei, Anhui, 230601, PR China. Electronic address: liuzhihua@hfut.edu.cn.
  • Wang HL; School of Food and Biological Engineering, Hefei University of Technology, No 485 Danxia Road, Hefei, Anhui, 230601, PR China. Electronic address: wanghl@hfut.edu.cn.
Free Radic Biol Med ; 211: 63-76, 2024 02 01.
Article en En | MEDLINE | ID: mdl-38092273
Ferroptosis, a new type of cell death accompanied by iron accumulation and lipid peroxidation, is implicated in the pathology of Parkinson's disease (PD), which is a prevalent neurodegenerative disorder that primarily occurred in the elderly population. Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea with known neuroprotective effects in PD patients. But whether EGCG-mediated neuroprotection against PD involves regulation of ferroptosis has not been elucidated. In this study, we established a PD model using PINK1 mutant Drosophila. Iron accumulation, lipid peroxidation and decreased activity of GPX, were detected in the brains of PD flies. Additionally, phenotypes of PD, including behavioral defects and dopaminergic neurons loss, were ameliorated by ferroptosis inhibitor ferrostatin-1 (Fer-1). Notably, the increased iron level, lipid peroxidation and decreased GPX activity in the brains of PD flies were relieved by EGCG. We found that EGCG exerted neuroprotection mainly by restoring iron homeostasis in the PD flies. EGCG inhibited iron influx by suppressing Malvolio (Mvl) expression and simultaneously promoted the upregulation of ferritin, the intracellular iron storage protein, leading to a reduction in free iron ions. Additionally, EGCG downregulated the expression of Duox and Nox, two NADPH oxidases that produce reactive oxygen species (ROS) and increased SOD enzyme activity. Finally, modulation of intracellular iron levels or regulation of oxidative stress by genetic means exerted great influence on PD phenotypes. As such, the results demonstrated that ferroptosis has a role in the established PD model. Altogether, EGCG has therapeutic potentials for treating PD by targeting the ferroptosis pathway, providing new strategies for the prevention and treatment of PD and other neurodegenerative diseases.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Enfermedades Neurodegenerativas / Proteínas de Drosophila / Ferroptosis Límite: Aged / Animals / Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Enfermedades Neurodegenerativas / Proteínas de Drosophila / Ferroptosis Límite: Aged / Animals / Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos