{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:04:40Z","timestamp":1791601480074,"version":"4.3.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T00:00:00Z","timestamp":1536796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Union through the European social fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"Fundo Europeu de Desenvolvimento Regional","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004923","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000346","name":"Ataxia UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000346","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/133192\/2017"],"award-info":[{"award-number":["SFRH\/BD\/133192\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National funds to FCT \u2013 Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UID\/BIM\/04773\/2013 CBMR"],"award-info":[{"award-number":["UID\/BIM\/04773\/2013 CBMR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Machado\u2013Joseph disease (MJD) is a neurodegenerative disorder caused by an abnormal expansion of citosine-adenine-guanine trinucleotide repeats in the disease-causing gene. This mutation leads to an abnormal polyglutamine tract in the protein ataxin-3 (Atx3), resulting in formation of mutant Atx3 aggregates. Despite several attempts to develop a therapeutic option for MJD, currently there are no available therapies capable of delaying or stopping disease progression. Recently, our group reported that reducing the expression levels of mutant Atx3 lead to a mitigation of several MJD-related behavior and neuropathological abnormalities. Aiming a more rapid translation to the human clinics, in this study we investigate a pharmacological inhibitor of translation\u2014cordycepin\u2014in several preclinical models. We found that cordycepin treatment significantly reduced (i) the levels of mutant Atx3, (ii) the neuropathological abnormalities in a lentiviral mouse model, (iii) the motor and neuropathological deficits in a transgenic mouse model and (iv) the number of ubiquitin aggregates in a human neural model. We hypothesize that the effect of cordycepin is mediated by the increase of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) levels, which is accompanied by a reduction in the global translation levels and by a significant activation of the autophagy pathway. Overall, this study suggests that cordycepin might constitute an effective and safe therapeutic approach for MJD, and probably for the other polyglutamine diseases.<\/jats:p>","DOI":"10.1093\/hmg\/ddy328","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T07:42:26Z","timestamp":1536738146000},"page":"51-63","source":"Crossref","is-referenced-by-count":45,"title":["Cordycepin activates autophagy through AMPK phosphorylation to reduce abnormalities in Machado\u2013Joseph disease models"],"prefix":"10.1093","volume":"28","author":[{"given":"Adriana","family":"Marcelo","sequence":"first","affiliation":[{"name":"Centre for Biomedical Research (CBMR), University of Algarve, Portugal"},{"name":"Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Portugal"},{"name":"Algarve Biomedical Center (ABC), University of Algarve and University Hospital of Algarve, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipa","family":"Brito","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Carmo-Silva","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A","family":"Matos","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"},{"name":"Institute for Interdisciplinary Research, University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Alves-Cruzeiro","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Vasconcelos-Ferreira","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Koppenol","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research (CBMR), University of Algarve, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds Pereira","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-5292","authenticated-orcid":false,"given":"Cl\u00e9vio","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research (CBMR), University of Algarve, Portugal"},{"name":"Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Portugal"},{"name":"Algarve Biomedical Center (ABC), University of Algarve and University Hospital of Algarve, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,13]]},"reference":[{"key":"2019102302291559500_ref1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0003341","article-title":"Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado\u2013Joseph disease","volume":"3","author":"Alves","year":"2008","journal-title":"PLoS One"},{"key":"2019102302291559500_ref2","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1093\/hmg\/ddn106","article-title":"Striatal and nigral pathology in a lentiviral rat model of Machado\u2013Joseph disease","volume":"17","author":"Alves","year":"2008","journal-title":"Hum. 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