{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:01:58Z","timestamp":1791270118298,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T00:00:00Z","timestamp":1457654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS056181"],"award-info":[{"award-number":["NS056181"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The gut hormone ghrelin is widely beneficial in many disease states. However, ghrelin exists in two distinctive isoforms, each with its own metabolic profile. In Parkinson's Disease (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) acylated ghrelin administration is neuroprotective, however, the role of des\u2010acylated ghrelin remains unknown. In this study, we wanted to identify the relative contribution each isoform plays using the <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> model of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. Chronic administration of acylated ghrelin in mice lacking both isoforms of ghrelin (Ghrelin <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) attenuated the <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>\u2010induced loss on tyrosine hydroxylase (<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>) neuronal number and volume and <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> protein expression in the nigrostriatal pathway. Moreover, acylated ghrelin reduced the increase in glial fibrillary acidic protein and Ionized calcium binding adaptor molecule 1 microglia in the substantia nigra. However, injection of acylated ghrelin also elevated plasma des\u2010acylated ghrelin, indicating <jats:italic>in\u00a0vivo<\/jats:italic> deacetylation. Next, we chronically administered des\u2010acylated ghrelin to Ghrelin <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice and observed no neuroprotective effects in terms of <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> cell number, <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> protein expression, glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 cell number. The lack of a protective effect was mirrored in ghrelin\u2010<jats:italic>O<\/jats:italic>\u2010acyltransferase <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice, which lack the ability to acylate ghrelin and consequently these mice have chronically increased plasma des\u2010acyl ghrelin. Plasma corticosterone was elevated in ghrelin\u2010<jats:italic>O<\/jats:italic>\u2010acyltransferase <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice and with des\u2010acylated ghrelin administration. Overall, our studies suggest that acylated ghrelin is the isoform responsible for <jats:italic>in\u00a0vivo<\/jats:italic> neuroprotection and that pharmacological approaches preventing plasma conversion from acyl ghrelin to des\u2010acyl ghrelin may have clinical efficacy to help slow or prevent the debilitating effects of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13576-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Ghrelin exists in the plasma as acyl and des\u2010acyl ghrelin. We determined the form responsible for <jats:italic>in\u00a0vivo<\/jats:italic> neuroprotection in a mouse model of Parkinson's disease. Although exogenous acyl ghrelin is deacylated <jats:italic>in\u00a0situ<\/jats:italic> to des\u2010acyl, only acyl ghrelin was neuroprotective by attenuating dopamine cell loss and glial activation. Acyl ghrelin is a therapeutic option to reduce Parkinson's Disease progression.<\/jats:p><jats:p><jats:bold>Cover Image<\/jats:bold> for this issue: doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1111\/jnc.13316\">10.1111\/jnc.13316<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13576","type":"journal-article","created":{"date-parts":[[2016,2,12]],"date-time":"2016-02-12T15:55:14Z","timestamp":1455292514000},"page":"460-471","source":"Crossref","is-referenced-by-count":51,"title":["Acylated but not des\u2010acyl ghrelin is neuroprotective in an <scp>MPTP<\/scp> mouse model of Parkinson's disease"],"prefix":"10.1111","volume":"137","author":[{"given":"Jacqueline A.","family":"Bayliss","sequence":"first","affiliation":[{"name":"Department of Physiology School of Biomedical and Psychological Sciences Monash University Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moyra","family":"Lemus","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Biomedical and Psychological Sciences Monash University Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa V.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Biomedical and Psychological Sciences Monash University Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh","family":"Deo","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Biomedical and Psychological Sciences Monash University Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Elsworth","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane B.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Biomedical and Psychological Sciences Monash University Melbourne Vic. 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