{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T02:47:16Z","timestamp":1782269236784,"version":"3.54.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T00:00:00Z","timestamp":1453852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0145425","type":"journal-article","created":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T18:35:37Z","timestamp":1453919737000},"page":"e0145425","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington\u2019s Disease Mice"],"prefix":"10.1371","volume":"11","author":[{"given":"Raffaella","family":"Tulino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnesska C.","family":"Benjamin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Jolinon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo N.","family":"Chini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisia","family":"Carnemolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian P.","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,1,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group","volume":"72","year":"1993","journal-title":"Cell"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"c3109","DOI":"10.1136\/bmj.c3109","article-title":"Huntington's disease","volume":"340","author":"MJ Novak","year":"2010","journal-title":"BMJ"},{"key":"ref3","first-page":"185","article-title":"Huntington's Disease","author":"HJ Waldvogel","year":"2014"},{"key":"ref4","first-page":"410","article-title":"Huntington's Disease","author":"GP Bates","year":"2014"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice","volume":"87","author":"L Mangiarini","year":"1996","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1073\/pnas.1221891110","article-title":"Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease","volume":"110","author":"K Sathasivam","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/hmg\/10.2.137","article-title":"Neurological abnormalities in a knock-in mouse model of Huntington's disease","volume":"10","author":"CH Lin","year":"2001","journal-title":"Hum Mol Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"8808","DOI":"10.1074\/jbc.M109.075028","article-title":"Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease","volume":"285","author":"C Landles","year":"2010","journal-title":"J Biol Chem"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.brainresbull.2006.11.004","article-title":"The Hdh(Q150\/Q150) knock-in mouse model of HD and the R6\/2 exon 1 model develop comparable and widespread molecular phenotypes","volume":"72","author":"B Woodman","year":"2007","journal-title":"Brain Res Bull"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"e8025","DOI":"10.1371\/journal.pone.0008025","article-title":"Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease","volume":"4","author":"H Moffitt","year":"2009","journal-title":"PLoS One"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1093\/hmg\/ddm133","article-title":"Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage","volume":"16","author":"A Kuhn","year":"2007","journal-title":"Hum Mol Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1172\/JCI57413","article-title":"Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease","volume":"121","author":"J Labbadia","year":"2011","journal-title":"J Clin Invest"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e1004550","DOI":"10.1371\/journal.pgen.1004550","article-title":"Dysfunction of the CNS-heart axis in mouse models of Huntington's disease","volume":"10","author":"M Mielcarek","year":"2014","journal-title":"PLoS Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e1005021","DOI":"10.1371\/journal.pgen.1005021","article-title":"HDAC4-myogenin axis as an important marker of HD-related skeletal muscle atrophy","volume":"11","author":"M Mielcarek","year":"2015","journal-title":"PLoS Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1126\/science.1099196","article-title":"Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase","volume":"305","author":"HY Cohen","year":"2004","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"429","DOI":"10.5483\/BMBRep.2013.46.9.180","article-title":"Emerging role of sirtuins on tumorigenesis: possible link between aging and cancer","volume":"46","author":"YI Cha","year":"2013","journal-title":"BMB Rep"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nature03354","article-title":"Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1","volume":"434","author":"JT Rodgers","year":"2005","journal-title":"Nature"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrc2562","article-title":"How does SIRT1 affect metabolism, senescence and cancer?","volume":"9","author":"CL Brooks","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1172\/JCI39319","article-title":"Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice","volume":"120","author":"C Escande","year":"2010","journal-title":"J Clin Invest"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"23489","DOI":"10.1074\/jbc.M112.365874","article-title":"Role of deleted in breast cancer 1 (DBC1) protein in SIRT1 deacetylase activation induced by protein kinase A and AMP-activated protein kinase","volume":"287","author":"V Nin","year":"2012","journal-title":"J Biol Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"E751","DOI":"10.1152\/ajpendo.00745.2009","article-title":"AMPK and SIRT1: a long-standing partnership?","volume":"298","author":"NB Ruderman","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1038\/sj.emboj.7601758","article-title":"SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis","volume":"26","author":"D Kim","year":"2007","journal-title":"EMBO J"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1523\/JNEUROSCI.3442-11.2012","article-title":"SIRT1 protects against alpha-synuclein aggregation by activating molecular chaperones","volume":"32","author":"G Donmez","year":"2012","journal-title":"J Neurosci"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/ng1534","article-title":"Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons","volume":"37","author":"JA Parker","year":"2005","journal-title":"Nat Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nm.2558","article-title":"Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets","volume":"18","author":"M Jiang","year":"2012","journal-title":"Nat Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nm.2559","article-title":"Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway","volume":"18","author":"H Jeong","year":"2012","journal-title":"Nat Med"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/acn3.135","article-title":"Sirtuin 1 activator SRT2104 protects Huntington's disease mice","volume":"1","author":"M Jiang","year":"2014","journal-title":"Ann Clin Transl Neurol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1365-2125.2012.04340.x","article-title":"Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man","volume":"75","author":"E Hoffmann","year":"2013","journal-title":"Br J Clin Pharmacol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1093\/hmg\/ddu010","article-title":"A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease","volume":"23","author":"MR Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/bcp.12512","article-title":"An exploratory double-blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington's disease","volume":"79","author":"SD Sussmuth","year":"2015","journal-title":"Br J Clin Pharmacol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nature06500","article-title":"DBC1 is a negative regulator of SIRT1","volume":"451","author":"JE Kim","year":"2008","journal-title":"Nature"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/hmg\/ddp467","article-title":"Identical oligomeric and fibrillar structures captured from the brains of R6\/2 and knock-in mouse models of Huntington's disease","volume":"19","author":"K Sathasivam","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1186\/bcr1632","article-title":"SirT1 modulates the estrogen-insulin-like growth factor-1 signaling for postnatal development of mammary gland in mice","volume":"9","author":"H Li","year":"2007","journal-title":"Breast Cancer Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"10220","DOI":"10.1523\/JNEUROSCI.1385-10.2010","article-title":"SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus","volume":"30","author":"A Satoh","year":"2010","journal-title":"J Neurosci"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1073\/pnas.0437870100","article-title":"Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease","volume":"100","author":"E Hockly","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.nbd.2005.07.007","article-title":"Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's disease","volume":"21","author":"E Hockly","year":"2006","journal-title":"Neurobiol Dis"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0361-9230(03)00185-0","article-title":"Standardization and statistical approaches to therapeutic trials in the R6\/2 mouse","volume":"61","author":"E Hockly","year":"2003","journal-title":"Brain Res Bull"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1326-3-17","article-title":"Optimisation of region-specific reference gene selection and relative gene expression analysis methods for pre-clinical trials of Huntington's disease","volume":"3","author":"CL Benn","year":"2008","journal-title":"Mol Neurodegener"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1093\/emboj\/21.10.2383","article-title":"Human SIR2 deacetylates p53 and antagonizes PML\/p53-induced cellular senescence","volume":"21","author":"E Langley","year":"2002","journal-title":"EMBO J"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1128\/MCB.26.1.28-38.2006","article-title":"Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage","volume":"26","author":"JM Solomon","year":"2006","journal-title":"Mol Cell Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"e4020","DOI":"10.1371\/journal.pone.0004020","article-title":"Phosphorylation regulates SIRT1 function","volume":"3","author":"T Sasaki","year":"2008","journal-title":"PLoS One"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1073\/pnas.91.2.714","article-title":"Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope","volume":"91","author":"JM Westendorf","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1042\/BST0370627","article-title":"The regulation of protein phosphorylation","volume":"37","author":"LN Johnson","year":"2009","journal-title":"Biochem Soc Trans"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"e8414","DOI":"10.1371\/journal.pone.0008414","article-title":"JNK1 phosphorylates SIRT1 and promotes its enzymatic activity","volume":"4","author":"N Nasrin","year":"2009","journal-title":"PLoS One"},{"key":"ref45","first-page":"245","article-title":"SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation","volume":"4","author":"AW Lau","year":"2014","journal-title":"Am J Cancer Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrn1587","article-title":"Modulation of neurodegeneration by molecular chaperones","volume":"6","author":"PJ Muchowski","year":"2005","journal-title":"Nat Rev Neurosci"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1091\/mbc.E03-07-0532","article-title":"Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones","volume":"15","author":"JF Morley","year":"2004","journal-title":"Mol Biol Cell"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4161\/pri.3.2.8587","article-title":"Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways","volume":"3","author":"PM Douglas","year":"2009","journal-title":"Prion"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/35099568","article-title":"Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila","volume":"413","author":"JS Steffan","year":"2001","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.bbrc.2009.02.085","article-title":"Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2","volume":"381","author":"B Zschoernig","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuron.2005.06.005","article-title":"p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease","volume":"47","author":"BI Bae","year":"2005","journal-title":"Neuron"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0150682","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T00:00:00Z","timestamp":1456444800000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0145425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T15:15:45Z","timestamp":1589037345000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0145425"}},"subtitle":[],"editor":[{"given":"Xiao-Jiang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,1,27]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,1,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0145425","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0150682","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,27]]}}}