Teaghrelin Protects SH-SY5Y Cells against MPP(+)-Induced Neurotoxicity through Activation of AMPK/SIRT1/PGC-1α and ERK1/2 Pathways

Teaghrelin 通过激活 AMPK/SIRT1/PGC-1α 和 ERK1/2 通路保护 SH-SY5Y 细胞免受 MPP(+) 诱导的神经毒性

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Abstract

The prevalence and incidence of Parkinson's disease (PD), an age-related neurodegenerative disease, are higher among elderly people. Independent of etiology, dysfunction and loss of dopaminergic neurons are common pathophysiological changes in PD patients with impaired motor and non-motor function. Currently, preventive or therapeutic treatment for combating PD is limited. The ghrelin axis and ghrelin receptor have been implicated in the preservation of dopaminergic neurons and have potential implications in PD treatment. Teaghrelin, a compound originating from Chin-Shin Oolong tea, exhibits ghrelin agonist activity. In this study, the neuroprotective potential of teaghrelin against PD was explored in a cell model in which human neuroblastoma SH-SY5Y cells were treated with the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP(+)). Upon MPP(+) exposure, SH-SY5Y cells exhibited decreased mitochondrial complex I activity and apoptotic cell death. Teaghrelin activated AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC-1α) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways to antagonize MPP(+)-induced cell death. Herein, we propose that teaghrelin is a potential candidate for the therapeutic treatment of PD.

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