Rapamycin reverses ferroptosis by increasing autophagy in MPTP/MPP+-induced models of Parkinson's disease

• Published in: Neural regeneration research Vol. 18; no. 11; pp. 2514 - 2519
• Main Authors: Liu, Tongyu, Wang, Peihan, Yin, Huan, Wang, Xiangfei, Lv, Jing, Yuan, Jiang, Zhu, Jing, Wang, Yunfu
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.11.2023; Medknow Publications & Media Pvt. Ltd; Wudang Mountain Hospital Area of Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,Shiyan,Hubei Province,China; Institute of Neuroscience,Hubei University of Medicine,Shiyan,Hubei Province,China; Institute of Neuroscience,Hubei University of Medicine,Shiyan,Hubei Province,China%Wudang Mountain Hospital Area of Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,Shiyan,Hubei Province,China%Department of Neurology,Affiliated Taihe Hospital,Hubei University of Medicine,Shiyan,Hubei Province,China%Department of Neurology,Affiliated Taihe Hospital,Hubei University of Medicine,Shiyan,Hubei Province,China; Department of Neurology,Affiliated Taihe Hospital,Hubei University of Medicine,Shiyan,Hubei Province,China; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Autophagy; autophagy; behavior; ferroptosis; mptp; parkinson’s disease; pc12 cell; rapamycin; tyrosine hydroxylase; Ferroptosis; Parkinson's disease; Reactive oxygen species; autophagy; ferroptosis; PC12 cell; MPTP; behavior; Parkinson’s disease; rapamycin; tyrosine hydroxylase; Parkinson's disease
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.371381

Parkinson's disease is a neurodegenerative disorder, and ferroptosis plays a significant role in the pathological mechanism underlying Parkinson's disease. Rapamycin, an autophagy inducer, has been shown to have neuroprotective effects in Parkinson's disease. However, the link between rapamycin and ferroptosis in Parkinson's disease is not entirely clear. In this study, rapamycin was administered to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model and a 1-methyl-4-phenylpyridinium-induced Parkinson's disease PC12 cell model. The results showed that rapamycin improved the behavioral symptoms of Parkinson's disease model mice, reduced the loss of dopamine neurons in the substantia nigra pars compacta, and reduced the expression of ferroptosis-related indicators (glutathione peroxidase 4, recombinant solute carrier family 7, member 11, glutathione, malondialdehyde, and reactive oxygen species). In the Parkinson's disease cell model, rapamycin improved cell viability and reduced ferroptosis. The neuroprotective effect of rapamycin was attenuated by a ferroptosis inducer (methyl (1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate) and an autophagy inhibitor (3-methyladenine). Inhibiting ferroptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects. Therefore, the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson's disease.