{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:28:09Z","timestamp":1787005689346,"version":"build-2736575974"},"reference-count":76,"publisher":"National Academy of Sciences","issue":"30","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100004089","name":"Krembil Foundation","doi-asserted-by":"publisher","award":["OG"],"award-info":[{"award-number":["OG"]}],"id":[{"id":"10.13039\/501100004089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000030","name":"Gouvernement du Canada | CIHR | Institute of Genetics","doi-asserted-by":"publisher","award":["MOP-119391"],"award-info":[{"award-number":["MOP-119391"]}],"id":[{"id":"10.13039\/501100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009836","name":"Huntington Society of Canada","doi-asserted-by":"publisher","award":["operation grant"],"award-info":[{"award-number":["operation grant"]}],"id":[{"id":"10.13039\/100009836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000887","name":"Huntington's Disease Society of America","doi-asserted-by":"publisher","award":["Berman Topper Fellowship"],"award-info":[{"award-number":["Berman Topper Fellowship"]}],"id":[{"id":"10.13039\/100000887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Doctoral Scholarship"],"award-info":[{"award-number":["Doctoral Scholarship"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,7,24]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>We have discovered a molecule derived from DNA-damage repair that can correct the lack of phosphorylation of mutant huntingtin, the cause of Huntington\u2019s disease (HD). In a mouse model, treatment reverses HD-like disease, and we see the lowering of mutant huntingtin levels to normal. The mechanism of this molecule is that it is processed to make a signal for kinase activity essential for repairing DNA. This mechanism is critical when neurons are stressed and have very low or absent energy levels. We propose that this molecule is a type of signaling from DNA-damage repair that occurs at dangerously low ATP levels.<\/jats:p>","DOI":"10.1073\/pnas.1801772115","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T15:15:41Z","timestamp":1531149341000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["N6-Furfuryladenine is protective in Huntington\u2019s disease models by signaling huntingtin phosphorylation"],"prefix":"10.1073","volume":"115","author":[{"given":"Laura E.","family":"Bowie","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Maiuri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Alpaugh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2R3, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Western University, London, ON N6A 3K7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-192X","authenticated-orcid":false,"given":"Nicolas","family":"Arbez","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Galleguillos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2R3, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L. K.","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianrun","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas T.","family":"Hertz","sequence":"additional","affiliation":[{"name":"Mitokinin, LLC, New York, NY 10006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Litchfield","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Western University, London, ON N6A 3K7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Sipione","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2R3, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2542-6641","authenticated-orcid":false,"given":"Ray","family":"Truant","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,7,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.018"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30161-8"},{"key":"e_1_3_3_5_2","first-page":"395","article-title":"Huntingtin is a scaffolding protein in the ATM oxidative DNA damage response complex","volume":"26","author":"Maiuri T","year":"2017","unstructured":"T Maiuri, , Huntingtin is a scaffolding protein in the ATM oxidative DNA damage response complex. Hum Mol Genet 26, 395\u2013406 (2017).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2009"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm217"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.03.009"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.20139"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2003.207.pe48"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw234"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.020"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.582"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.06.030"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds554"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.01.008"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0063-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1114502109"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","unstructured":"CLK Hung A patient-derived cellular model for Huntington disease reveals phenotypes at clinically relevant CAG lengths. bioRxiv:10.1101\/291575. Preprint posted March 29 2018. (2018).","DOI":"10.1101\/291575"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2006.06.024"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1669"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1752"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007058602594"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3928"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.030"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi319"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(95)00015-9"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802611795347645"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.002931"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200909067"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr333"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301342110"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.19.2799"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2097"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e31822e1825"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168386"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-015-2642-5"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088284"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg169"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/70033"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.067"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph10010027"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1139\/o04-116"},{"key":"e_1_3_3_44_2","first-page":"49","article-title":"Protein kinase CK2 in DNA damage and repair","volume":"5","author":"Montenarh M","year":"2016","unstructured":"M Montenarh, Protein kinase CK2 in DNA damage and repair. Transl Cancer Res 5, 49\u201363 (2016).","journal-title":"Transl Cancer Res"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2014.03.022"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/sageke.2004.22.pe24"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.11.008"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(02)00622-X"},{"key":"e_1_3_3_49_2","first-page":"TF01","article-title":"Evaluation of the potency of kinetin on radiation induced behavioural changes in Swiss albino mice","volume":"11","author":"Radhakrishna V","year":"2017","unstructured":"V Radhakrishna, , Evaluation of the potency of kinetin on radiation induced behavioural changes in Swiss albino mice. J Clin Diagn Res 11, TF01\u2013TF04 (2017).","journal-title":"J Clin Diagn Res"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2727"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.02.006"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-160205"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw051"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep03631"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-017-9811-0"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2017.08.014"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81782-1"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80339"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.09.007"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.782300"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25143"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970759w"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-150169"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa0441"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01037-5"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9845"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45691"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu460"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-07-0433"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.2174\/156652411794474419"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2016.07.009"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-381298-8.00023-X"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(02)00137-0"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2001682"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/266730a0"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(99)09026-6"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1801772115","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1801772115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T03:46:59Z","timestamp":1649821619000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1801772115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,9]]},"references-count":76,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2018,7,24]]}},"alternative-id":["10.1073\/pnas.1801772115"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1801772115","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,9]]},"assertion":[{"value":"2018-07-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}