Teaghrelin protected dopaminergic neurons in MPTP‐induced Parkinson's disease animal model by promoting PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC1‐α‐mediated mitochondrial biogenesis

Abstract Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD. Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD.