Neuroprotective effects of cordycepin on MPTP-induced Parkinson's disease mice via suppressing PI3K/AKT/mTOR and MAPK-mediated neuroinflammation

被引:7
|
作者
Wang, Linhai [1 ,2 ]
Tian, Shu [3 ]
Ruan, Sisi [1 ,2 ]
Wei, Jingjing [1 ,2 ]
Wei, Sijia [4 ]
Chen, Weiwei [5 ]
Hu, Hangcui [5 ]
Qin, Weiwei [6 ]
Li, Yan [1 ]
Yuan, Hang [1 ]
Mao, Jian [1 ,2 ]
Xu, Yan [5 ]
Xie, Jianping [1 ,2 ]
机构
[1] Zhengzhou Univ, Coll Chem, Flavour Sci Res Ctr, Zhengzhou, Peoples R China
[2] Beijing Life Sci Acad BLSA, Beijing, Peoples R China
[3] Inner Mongolia Kunming Cigarette LLC Co, Hohhot, Inner Mongolia, Peoples R China
[4] Xinxiang Cent Hosp, Xinxiang, Peoples R China
[5] Zhengzhou Univ, Sch Basic Med Sci, Dept Med Genet & Cell Biol, Zhengzhou, Peoples R China
[6] Henan Prov Peoples Hosp, Dept Neurol, State Key Clin Specialty, Minist Hlth Neurol, Zhengzhou, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Cordycepin; Parkinson 's disease; Microglia; Proteomics and phosphoproteomics; PI3K/AKT/mTOR; MAPK; AUTOPHAGY; MODULATION; ACTIVATION; CROSSTALK; MODELS; ROLES; NOTCH;
D O I
10.1016/j.freeradbiomed.2024.02.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Parkinson 's disease (PD) is a prevalent progressive and multifactorial neurodegenerative disorder. Cordycepin is known to exhibit antitumor, anti-inflammatory, antioxidative stress, and neuroprotective effects; however, few studies have explored the neuroprotective mechanism of cordycepin in PD. Using a 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced mouse model, we investigated the impact of cordycepin on PD and its underlying molecular mechanisms. The findings indicated that cordycepin significantly mitigated MPTP-induced behavior disorder and neuroapoptosis, diminished the loss of dopaminergic neurons in the striatum -substantia nigra pathway, elevated striatal monoamine levels and its metabolites, and inhibited the polarization of microglia and the expression of pro-inflammatory factors. Subsequent proteomic and phosphoproteomic analyses revealed the involvement of the MAPK, mTOR, and PI3K/AKT signaling pathways in the protective mechanism of cordycepin. Cordycepin treatment inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the expression of autophagy proteins in the striatum and substantia nigra. We also demonstrated the in vivo inhibition of the ERK/JNK signaling pathway by cordycepin treatment. In summary, our investigation reveals that cordycepin exerts neuroprotective effects against PD by promoting autophagy and suppressing neuroinflammation and neuronal apoptosis by inhibiting the PI3K/AKT/mTOR and ERK/JNK signaling pathways. This finding highlights the favorable characteristics of cordycepin in neuroprotection and provides novel molecular insights into the neuroprotective role of natural products in PD.
引用
收藏
页码:60 / 77
页数:18
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