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Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH\u2010SY5Y cells against 1\u2010methyl\u20104\u2010phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK\/SIRT1\/PGC\u20101\u03b1 pathway. In this study, an animal model was established using a neurotoxin, 1\u2010methyl\u20104phenyl\u20101,2,3,6\u2010tetrahydropyridine (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\u2010induced 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\u2010treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of \u03b1Syn and apoptosis\u2010related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP\u2010treated mice by increasing PINK1\/Parkin\u2010mediated mitophagy and AMPK\/SIRT1\/PGC\u20101\u03b1\u2010mediated 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\u2010SY5Y cells against 1\u2010methyl\u20104\u2010phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK\/SIRT1\/PGC\u20101\u03b1 pathway. In this study, an animal model was established using a neurotoxin, 1\u2010methyl\u20104phenyl\u20101,2,3,6\u2010tetrahydropyridine (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\u2010induced 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\u2010treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of \u03b1Syn and apoptosis\u2010related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP\u2010treated mice by increasing PINK1\/Parkin\u2010mediated mitophagy and AMPK\/SIRT1\/PGC\u20101\u03b1\u2010mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD.<\/jats:p>","DOI":"10.1002\/tox.24275","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T04:34:35Z","timestamp":1713242075000},"page":"4022-4034","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Teaghrelin protected dopaminergic neurons in <scp>MPTP<\/scp>\u2010induced Parkinson's disease animal model by promoting <scp>PINK1<\/scp>\/Parkin\u2010mediated mitophagy and <scp>AMPK<\/scp>\/<scp>SIRT1<\/scp>\/<scp>PGC1<\/scp>\u2010\u03b1\u2010mediated mitochondrial biogenesis"],"prefix":"10.1002","volume":"39","author":[{"given":"Cian\u2010Fen","family":"Jhuo","sequence":"first","affiliation":[{"name":"Graduate Institute of Biotechnology, National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research Taichung Veterans General Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason T.C.","family":"Tzen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biotechnology, National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-5285","authenticated-orcid":false,"given":"Wen\u2010Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine National Chung Hsing University  Taichung 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