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.

AIMS:We performed cell and animal experiments to explore the therapeutic effect of artemisinin on Parkinson's disease (PD) and the TLR4/Myd88 signaling pathway. METHODS:C57 mice were randomly divided into the blank, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced and artemisinin-treated groups. Clinical symptoms, the number of dopaminergic (DAergic) neurons in the substantia nigra, and microglial cell activation were compared among the three groups. Subsequently, BV-2 cell activation and TLR4/Myd88 pathway component expression were compared among the blank, MPP+ -treated, artemisinin-treated, and TLR4 activator-treated groups. RESULTS:Behavioral symptoms were improved, the number of DAergic neurons in the substantia nigra of the midbrain was increased, and microglial cell activation was decreased in artemisinin-treated MPTP-induced PD model mice compared with control-treated MPTP-induced PD model mice (p < 0.05). The cell experiments revealed that artemisinin treatment reduced MPP+ -induced BV-2 cell activation and inhibited the TLR4/Myd88 signaling pathway. Moreover, the effect of artemisinin on the BV-2 cell model was inhibited by the TLR4 activator LPS (p < 0.05). CONCLUSION:Artemisinin may reduce damage to DAergic neurons in a PD mouse model by decreasing microglial activation through the TLR4-mediated MyD88-dependent signaling pathway. However, this finding cannot explain the relationship between microglia and DAergic neurons.

重症肌无力(myasthenia gravis,MG)是一种由体液免疫和细胞免疫参与,抗体和补体介导的神经肌肉接头(neuromuscular junction,NMJ)处传递功能障碍引起的自身免疫性疾病. MG的典型临床特征是部分或全身骨骼肌无力和易疲劳,并伴有活动后症状加重、休息后缓解的临床表现[1] .