{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:57:51Z","timestamp":1779321471310,"version":"3.51.4"},"reference-count":66,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":504,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171394"],"award-info":[{"award-number":["82171394"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671235"],"award-info":[{"award-number":["81671235"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taishan Scholars Program of Shandong Province"},{"DOI":"10.13039\/100019558","name":"Qingdao Key Health Discipline Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019558","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Qingdao Technology Program for Health and Welfare","award":["20-3-4-42-nsh"],"award-info":[{"award-number":["20-3-4-42-nsh"]}]}],"content-domain":{"domain":["neurotherapeuticsjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurotherapeutics"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1007\/s13311-022-01216-9","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T14:06:53Z","timestamp":1648217213000},"page":"994-1006","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bezafibrate Rescues Mitochondrial Encephalopathy in Mice via Induction of Daily Torpor and Hypometabolic State"],"prefix":"10.1016","volume":"19","author":[{"given":"Jingwei","family":"Lyu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenfei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Xin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanzhu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9330-0405","authenticated-orcid":false,"given":"Kunqian","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1136\/jnnp.14.3.216","article-title":"Subacute necrotizing encephalomyelopathy in an infant","volume":"14","author":"Leigh","year":"1951","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/ana.75","article-title":"The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities","volume":"49","author":"Darin","year":"2001","journal-title":"Ann Neurol"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/ana.410390311","article-title":"Leigh syndrome: clinical features and biochemical and DNA abnormalities","volume":"39","author":"Rahman","year":"1996","journal-title":"Ann Neurol"},{"issue":"2","key":"10.1007\/s13311-022-01216-9_bib4","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/ana.24551","article-title":"Leigh syndrome: one disorder, more than 75 monogenic causes","volume":"79","author":"Lake","year":"2016","journal-title":"Ann Neurol"},{"issue":"6","key":"10.1007\/s13311-022-01216-9_bib5","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/NEN.0000000000000195","article-title":"Leigh syndrome: neuropathology and pathogenesis","volume":"74","author":"Lake","year":"2015","journal-title":"J Neuropathol Exp Neurol"},{"issue":"4","key":"10.1007\/s13311-022-01216-9_bib6","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s004010051007","article-title":"Adult Leigh syndrome with mitochondrial DNA mutation at 8993","volume":"97","author":"Nagashima","year":"1999","journal-title":"Acta Neuropathol"},{"issue":"11","key":"10.1007\/s13311-022-01216-9_bib7","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1016\/j.jocn.2014.03.020","article-title":"Adult onset Leigh syndrome with mitochondrial DNA 8344 A>G mutation","volume":"21","author":"Han","year":"2014","journal-title":"J Clin Neurosci"},{"issue":"2","key":"10.1007\/s13311-022-01216-9_bib8","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1212\/WNL.49.2.589","article-title":"A mitochondrial DNA tRNA(Val) point mutation associated with adult-onset Leigh syndrome","volume":"49","author":"Chalmers","year":"1997","journal-title":"Neurology"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/jnnp-2012-304426","article-title":"A guide to diagnosis and treatment of Leigh syndrome","volume":"85","author":"Baertling","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1007\/s13311-022-01216-9_bib10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1475-2840-4-14","article-title":"Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons","volume":"4","author":"Tenenbaum","year":"2005","journal-title":"Cardiovasc Diabetol"},{"issue":"4","key":"10.1007\/s13311-022-01216-9_bib11","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1210\/jc.2007-1701","article-title":"Activation of peroxisome proliferator-activated receptor pathway stimulates the mitochondrial respiratory chain and can correct deficiencies in patients' cells lacking its components","volume":"93","author":"Bastin","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"10.1007\/s13311-022-01216-9_bib12","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1124\/jpet.110.166504","article-title":"Bezafibrate mildly stimulates ketogenesis and fatty acid metabolism in hypertriglyceridemic subjects","volume":"334","author":"Tremblay-Mercier","year":"2010","journal-title":"J Pharmacol Exp Ther"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib13","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.nut.2015.05.015","article-title":"Ketogenic response to cotreatment with bezafibrate and medium chain triacylglycerols in healthy humans","volume":"31","author":"Courchesne-Loyer","year":"2015","journal-title":"Nutrition"},{"key":"10.1007\/s13311-022-01216-9_bib14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.mito.2016.09.003","article-title":"Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling","volume":"31","author":"Zielinski","year":"2016","journal-title":"Mitochondrion"},{"key":"10.1007\/s13311-022-01216-9_bib15","doi-asserted-by":"crossref","unstructured":"Djouadi F, Bastin J. Species differences in the effects of bezafibrate as a potential treatment of mitochondrial disorders. Cell Metab. 2011;14(6):715\u2013716.","DOI":"10.1016\/j.cmet.2011.11.003"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib16","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/hmg\/ddr482","article-title":"Effect of bezafibrate treatment on late-onset mitochondrial myopathy in mice","volume":"21","author":"Yatsuga","year":"2012","journal-title":"Hum Mol Genet"},{"key":"10.1007\/s13311-022-01216-9_bib17","doi-asserted-by":"crossref","unstructured":"Dillon LM, Hida A, Garcia S, Prolla TA, Moraes CT. Long-term bezafibrate treatment improves skin and spleen phenotypes of the mtDNA mutator mouse. PLoS One. 2012;7(9):e44335.","DOI":"10.1371\/journal.pone.0044335"},{"issue":"1","key":"10.1007\/s13311-022-01216-9_bib18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cmet.2011.04.011","article-title":"In vivo correction of COX deficiency by activation of the AMPK\/PGC-1alpha axis","volume":"14","author":"Viscomi","year":"2011","journal-title":"Cell Metab"},{"key":"10.1007\/s13311-022-01216-9_bib19","doi-asserted-by":"crossref","unstructured":"Frambach S, van de Wal MAE, van den Broek PHH, et al. Effects of clofibrate and KH176 on life span and motor function in mitochondrial complex I-deficient mice. Biochim Biophys Acta Mol Basis Dis. 2020;1866(6):165727.","DOI":"10.1016\/j.bbadis.2020.165727"},{"issue":"7","key":"10.1007\/s13311-022-01216-9_bib20","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1172\/JCI62923","article-title":"Fatal breathing dysfunction in a mouse model of Leigh syndrome","volume":"122","author":"Quintana","year":"2012","journal-title":"J Clin Invest"},{"issue":"24","key":"10.1007\/s13311-022-01216-9_bib21","doi-asserted-by":"crossref","first-page":"10996","DOI":"10.1073\/pnas.1006214107","article-title":"Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome","volume":"107","author":"Quintana","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"10.1007\/s13311-022-01216-9_bib22","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cmet.2008.02.004","article-title":"Mice with mitochondrial complex I deficiency develop a fatal encephalomyopathy","volume":"7","author":"Kruse","year":"2008","journal-title":"Cell Metab"},{"issue":"24","key":"10.1007\/s13311-022-01216-9_bib23","doi-asserted-by":"crossref","first-page":"20652","DOI":"10.1074\/jbc.M111.327601","article-title":"Proteomic and metabolomic analyses of mitochondrial complex I-deficient mouse model generated by spontaneous B2 short interspersed nuclear element (SINE) insertion into NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) gene","volume":"287","author":"Leong","year":"2012","journal-title":"J Biol Chem"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib24","doi-asserted-by":"crossref","first-page":"5262","DOI":"10.1210\/en.2008-0285","article-title":"Bezafibrate, a peroxisome proliferator-activated receptors agonist, decreases body temperature and enhances electroencephalogram delta-oscillation during sleep in mice","volume":"149","author":"Chikahisa","year":"2008","journal-title":"Endocrinology"},{"issue":"4","key":"10.1007\/s13311-022-01216-9_bib25","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1194\/jlr.M082040","article-title":"Low ketolytic enzyme levels in tumors predict ketogenic diet responses in cancer cell lines in vitro and in vivo","volume":"59","author":"Zhang","year":"2018","journal-title":"J Lipid Res"},{"issue":"6","key":"10.1007\/s13311-022-01216-9_bib26","doi-asserted-by":"crossref","first-page":"E418","DOI":"10.1152\/ajpendo.00319.2015","article-title":"Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD","volume":"310","author":"Luo","year":"2016","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10.1007\/s13311-022-01216-9_bib27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/978-1-61779-504-6_22","article-title":"Measurement of mitochondrial DNA copy number","volume":"837","author":"Venegas","year":"2012","journal-title":"Methods Mol Biol"},{"issue":"49","key":"10.1007\/s13311-022-01216-9_bib28","doi-asserted-by":"crossref","first-page":"20735","DOI":"10.1021\/jacs.0c09576","article-title":"Oxidative damage of tryptophan hydroxylase-2 mediated by peroxisomal superoxide anion radical in brains of mouse with depression","volume":"142","author":"Ding","year":"2020","journal-title":"J Am Chem Soc"},{"key":"10.1007\/s13311-022-01216-9_bib29","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0076-6879(00)19040-8","article-title":"Protein oxidative damage","volume":"319","author":"Shacter","year":"2000","journal-title":"Methods Enzymol"},{"issue":"6165","key":"10.1007\/s13311-022-01216-9_bib30","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1126\/science.1244360","article-title":"mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome","volume":"342","author":"Johnson","year":"2013","journal-title":"Science"},{"issue":"5","key":"10.1007\/s13311-022-01216-9_bib31","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1093\/hmg\/ddr541","article-title":"Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington's disease","volume":"21","author":"Johri","year":"2012","journal-title":"Hum Mol Genet"},{"issue":"23","key":"10.1007\/s13311-022-01216-9_bib32","doi-asserted-by":"crossref","first-page":"5091","DOI":"10.1093\/hmg\/dds355","article-title":"Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice","volume":"21","author":"Dumont","year":"2012","journal-title":"Hum Mol Genet"},{"issue":"4","key":"10.1007\/s13311-022-01216-9_bib33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jtherbio.2011.11.011","article-title":"Oral bezafibrate induces daily torpor and FGF21 in mice in a PPAR alpha dependent manner","volume":"37","author":"Lisa","year":"2012","journal-title":"J Therm Biol"},{"issue":"7","key":"10.1007\/s13311-022-01216-9_bib34","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.bcp.2008.06.017","article-title":"The pharmacology and molecular mechanisms underlying temperature regulation and torpor","volume":"76","author":"Swoap","year":"2008","journal-title":"Biochem Pharmacol"},{"issue":"5","key":"10.1007\/s13311-022-01216-9_bib35","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s10495-007-0756-2","article-title":"Mitochondria, oxidative stress and cell death","volume":"12","author":"Ott","year":"2007","journal-title":"Apoptosis"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib36","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","article-title":"The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase","volume":"247","author":"Misra","year":"1972","journal-title":"J Biol Chem"},{"issue":"6","key":"10.1007\/s13311-022-01216-9_bib37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4330\/wjc.v5.i6.164","article-title":"Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system","volume":"5","author":"Kim","year":"2013","journal-title":"World J Cardiol"},{"issue":"9","key":"10.1007\/s13311-022-01216-9_bib38","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/S1474-4422(11)70155-7","article-title":"FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study","volume":"10","author":"Suomalainen","year":"2011","journal-title":"Lancet Neurol"},{"issue":"21","key":"10.1007\/s13311-022-01216-9_bib39","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1212\/01.wnl.0000436068.43384.ef","article-title":"Fibroblast growth factor 21 is a sensitive biomarker of mitochondrial disease","volume":"81","author":"Davis","year":"2013","journal-title":"Neurology"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib40","doi-asserted-by":"crossref","first-page":"8110","DOI":"10.1007\/s12035-016-0283-7","article-title":"Growth differentiation factor 15 is a novel diagnostic biomarker of mitochondrial diseases","volume":"54","author":"Ji","year":"2017","journal-title":"Mol Neurobiol"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib41","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/ncpendmet0427","article-title":"Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1","volume":"3","author":"LeRoith","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab"},{"issue":"4\u20135","key":"10.1007\/s13311-022-01216-9_bib42","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000184187","article-title":"Hormonal and nutritional regulation of IGF-I and its binding proteins","volume":"42","author":"Underwood","year":"1994","journal-title":"Horm Res"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib43","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1210\/en.2002-220116","article-title":"Insights from insulin-like growth factor binding protein transgenic mice","volume":"143","author":"Silha","year":"2002","journal-title":"Endocrinology"},{"issue":"5","key":"10.1007\/s13311-022-01216-9_bib44","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0022-2275(20)42003-6","article-title":"Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression","volume":"37","author":"Schoonjans","year":"1996","journal-title":"J Lipid Res"},{"issue":"1","key":"10.1007\/s13311-022-01216-9_bib45","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11883-004-0115-5","article-title":"Fibrates for treatment of the metabolic syndrome","volume":"6","author":"Maki","year":"2004","journal-title":"Curr Atheroscler Rep"},{"key":"10.1007\/s13311-022-01216-9_bib46","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/8492353","article-title":"PPAR gamma and angiogenesis: endothelial cells perspective","volume":"2016","author":"Kotlinowski","year":"2016","journal-title":"J Diabetes Res"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib47","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.eplepsyres.2011.09.021","article-title":"Modulation of oxidative stress and mitochondrial function by the ketogenic diet","volume":"100","author":"Milder","year":"2012","journal-title":"Epilepsy Res"},{"issue":"28","key":"10.1007\/s13311-022-01216-9_bib48","doi-asserted-by":"crossref","first-page":"8714","DOI":"10.1073\/pnas.1509930112","article-title":"High-fat diet and FGF21 cooperatively promote aerobic thermogenesis in mtDNA mutator mice","volume":"112","author":"Wall","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib49","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1093\/hmg\/ddp093","article-title":"PGC-1alpha\/beta induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders","volume":"18","author":"Srivastava","year":"2009","journal-title":"Hum Mol Genet"},{"key":"10.1007\/s13311-022-01216-9_bib50","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1750-1172-7-21","article-title":"Copper and bezafibrate cooperate to rescue cytochrome c oxidase deficiency in cells of patients with SCO2 mutations","volume":"7","author":"Casarin","year":"2012","journal-title":"Orphanet J Rare Dis"},{"issue":"9","key":"10.1007\/s13311-022-01216-9_bib51","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.bbadis.2017.05.019","article-title":"Bezafibrate prevents mitochondrial dysfunction, antioxidant system disturbance, glial reactivity and neuronal damage induced by sulfite administration in striatum of rats: implications for a possible therapeutic strategy for sulfite oxidase deficiency","volume":"1863","author":"Grings","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib52","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.tem.2009.09.005","article-title":"Torpor induction in mammals: recent discoveries fueling new ideas","volume":"20","author":"Melvin","year":"2009","journal-title":"Trends Endocrinol Metab"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib53","doi-asserted-by":"crossref","first-page":"R769","DOI":"10.1152\/ajpregu.00131.2009","article-title":"Cardiovascular changes during daily torpor in the laboratory mouse","volume":"297","author":"Swoap","year":"2009","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib54","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.resp.2004.03.014","article-title":"Natural hypometabolism during hibernation and daily torpor in mammals","volume":"141","author":"Heldmaier","year":"2004","journal-title":"Respir Physiol Neurobiol"},{"issue":"1","key":"10.1007\/s13311-022-01216-9_bib55","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s12035-018-1074-0","article-title":"Bezafibrate prevents glycine-induced increase of antioxidant enzyme activities in rat striatum","volume":"56","author":"Parmeggiani","year":"2019","journal-title":"Mol Neurobiol"},{"key":"10.1007\/s13311-022-01216-9_bib56","doi-asserted-by":"crossref","unstructured":"Ishida N. Role of PPAR\u03b1 in the control of torpor through FGF21-NPY pathway: From circadian clock to seasonal change in mammals. PPAR Res. 2009;412949.","DOI":"10.1155\/2009\/412949"},{"key":"10.1007\/s13311-022-01216-9_bib57","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-physiol-021115-105339","article-title":"Understanding the physiology of FGF21","volume":"78","author":"Fisher","year":"2016","journal-title":"Annu Rev Physiol"},{"issue":"2","key":"10.1007\/s13311-022-01216-9_bib58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.cmet.2008.06.014","article-title":"The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man","volume":"8","author":"G\u00e4lman","year":"2008","journal-title":"Cell Metab"},{"key":"10.1007\/s13311-022-01216-9_bib59","doi-asserted-by":"crossref","unstructured":"Steele H, Gomez-Duran A, Pyle A, et al. Metabolic effects of bezafibrate in mitochondrial disease. EMBO Mol Med. 2020;12(3):e11589.","DOI":"10.15252\/emmm.201911589"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib60","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/nm.4392","article-title":"GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates","volume":"23","author":"Mullican","year":"2017","journal-title":"Nat Med"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib61","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1038\/nm.4393","article-title":"The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL","volume":"23","author":"Emmerson","year":"2017","journal-title":"Nat Med"},{"issue":"10","key":"10.1007\/s13311-022-01216-9_bib62","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1038\/nm.4394","article-title":"GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand","volume":"23","author":"Yang","year":"2017","journal-title":"Nat Med"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib63","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/eci.12591","article-title":"Ketogenic diets: from cancer to mitochondrial diseases and beyond","volume":"46","author":"Branco","year":"2016","journal-title":"Eur J Clin Invest"},{"issue":"1","key":"10.1007\/s13311-022-01216-9_bib64","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s42255-020-00334-y","article-title":"Tetracyclines promote survival and fitness in mitochondrial disease models","volume":"3","author":"Perry","year":"2021","journal-title":"Nat Metab"},{"issue":"3","key":"10.1007\/s13311-022-01216-9_bib65","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s13311-014-0285-y","article-title":"PARP inhibition delays progression of mitochondrial encephalopathy in mice","volume":"11","author":"Felici","year":"2014","journal-title":"Neurotherapeutics"},{"issue":"6281","key":"10.1007\/s13311-022-01216-9_bib66","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.aad9642","article-title":"Hypoxia as a therapy for mitochondrial disease","volume":"352","author":"Jain","year":"2016","journal-title":"Science"}],"container-title":["Neurotherapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-022-01216-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13311-022-01216-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923011182?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923011182?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-022-01216-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T07:01:58Z","timestamp":1761807718000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1878747923011182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["S1878747923011182"],"URL":"https:\/\/doi.org\/10.1007\/s13311-022-01216-9","relation":{},"ISSN":["1878-7479"],"issn-type":[{"value":"1878-7479","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bezafibrate Rescues Mitochondrial Encephalopathy in Mice via Induction of Daily Torpor and Hypometabolic State","name":"articletitle","label":"Article Title"},{"value":"Neurotherapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1007\/s13311-022-01216-9","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2022 The American Society for Experimental NeuroTherapeutics, Inc. Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}