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

作　　者：Tongyu Liu Peihan Wang Huan Yin Xiangfei Wang Jing Lv Jiang Yuan Jing Zhu Yunfu Wang 

机构地区：[1]Department of Neurology,Affiliated Taihe Hospital,Hubei University of Medicine,Shiyan,Hubei Province,China [2]Institute of Neuroscience,Hubei University of Medicine,Shiyan,Hubei Province,China [3]Wudang Mountain Hospital Area of Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,Shiyan,Hubei Province,China

出　　处：《Neural Regeneration Research》2023年第11期2514-2519,共6页中国神经再生研究（英文版）

摘　　要：Parkinson’s disease is a neurodegenerative disorder,and fe rroptosis 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 administe red 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 ferro ptosis.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 ferro ptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects.Therefo re,the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson’s disease.

关 键 词：AUTOPHAGY behavior ferroptosis MPTP Parkinson’s disease PC12 cell RAPAMYCIN tyrosine hydroxylase 

分 类 号：R742.5[医药卫生—神经病学与精神病学]