{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:41:13Z","timestamp":1788381673224,"version":"build-2803163510"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["PrometeoII\/2014\/029"],"award-info":[{"award-number":["PrometeoII\/2014\/029"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Mol Med"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1038\/s12276-019-0264-9","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T07:03:09Z","timestamp":1559718189000},"page":"1-16","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Metformin treatment reduces motor and neuropsychiatric phenotypes in the zQ175 mouse model of Huntington disease"],"prefix":"10.1038","volume":"51","author":[{"given":"Ana","family":"Sanchis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Adelaida","family":"Garc\u00eda-Gimeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8709-6345","authenticated-orcid":false,"given":"Antonio Jos\u00e9","family":"Ca\u00f1ada-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Sequedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Mill\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascual","family":"Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0033","authenticated-orcid":false,"given":"Rafael P.","family":"V\u00e1zquez-Manrique","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"264_CR1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.biocel.2010.10.014","volume":"43","author":"S Krobitsch","year":"2011","unstructured":"Krobitsch, S. & Kazantsev, A. G. Huntington's disease: from molecular basis to therapeutic advances. Int. J. Biochem. Cell Biol. 43, 20\u201324 (2011).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"264_CR2","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1523\/JNEUROSCI.11-12-03877.1991","volume":"11","author":"RJ Ferrante","year":"1991","unstructured":"Ferrante, R. J., Kowall, N. W. & Richardson, E. P. Jr Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J. Neurosci. 11, 3877\u20133887 (1991).","journal-title":"J. Neurosci."},{"key":"264_CR3","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1083\/jcb.200510065","volume":"172","author":"A Yamamoto","year":"2006","unstructured":"Yamamoto, A., Cremona, M. L. & Rothman, J. E. Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway. J. Cell Biol. 172, 719\u2013731 (2006).","journal-title":"J. Cell Biol."},{"key":"264_CR4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnmol.2014.00077","volume":"7","author":"Z Ortega","year":"2014","unstructured":"Ortega, Z. & Lucas, J. J. Ubiquitin-proteasome system involvement in Huntington\u2019s disease. Front. Mol. Neurosci. 7, 77 (2014).","journal-title":"Front. Mol. Neurosci."},{"key":"264_CR5","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/emboj.2009.8","volume":"28","author":"G Herrero-Martin","year":"2009","unstructured":"Herrero-Martin, G. et al. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J. 28, 677\u2013685 (2009).","journal-title":"EMBO J."},{"key":"264_CR6","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/ncb1537","volume":"9","author":"J Liang","year":"2007","unstructured":"Liang, J. et al. The energy sensing LKB1-AMPK pathway regulatesp27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat. Cell Biol. 9, 218\u2013224 (2007).","journal-title":"Nat. Cell Biol."},{"key":"264_CR7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1042\/BJ20120546","volume":"445","author":"D Carling","year":"2012","unstructured":"Carling, D., Thornton, C., Woods, A. & Sanders, M. J. AMP-activated protein kinase: new regulation, new roles? Biochem. J. 445, 11\u201327 (2012).","journal-title":"Biochem. J."},{"key":"264_CR8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1152\/physiol.00050.2013","volume":"29","author":"DG Hardie","year":"2014","unstructured":"Hardie, D. G. & Ashford, M. L. AMPK: regulating energy balance at the cellular and whole body levels. Physiology 29, 99\u2013107 (2014).","journal-title":"Physiology"},{"key":"264_CR9","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1093\/hmg\/ddv513","volume":"25","author":"RP Vazquez-Manrique","year":"2015","unstructured":"Vazquez-Manrique, R. P. et al. AMPK activation protects from neuronal dysfunction and vulnerability across nematode, cellular and mouse models of Huntington's disease. Hum. Mol. Genet. 25, 1043\u20131058 (2015).","journal-title":"Hum. Mol. Genet."},{"key":"264_CR10","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1073\/pnas.0501507102","volume":"102","author":"SQ Harper","year":"2005","unstructured":"Harper, S. Q. et al. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl. Acad. Sci. USA 102, 5820\u20135825 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"264_CR11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)80623-6","volume":"101","author":"A Yamamoto","year":"2000","unstructured":"Yamamoto, A., Lucas, J. J. & Hen, R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101, 57\u201366 (2000).","journal-title":"Cell"},{"key":"264_CR12","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1126\/science.1120781","volume":"310","author":"RJ Shaw","year":"2005","unstructured":"Shaw, R. J. et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310, 1642\u20131646 (2005).","journal-title":"Science"},{"key":"264_CR13","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1172\/JCI13505","volume":"108","author":"G Zhou","year":"2001","unstructured":"Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167\u20131174 (2001).","journal-title":"J. Clin. Invest."},{"key":"264_CR14","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1172\/JCI14178","volume":"108","author":"LA Witters","year":"2001","unstructured":"Witters, L. A. The blooming of the French lilac. J. Clin. Invest. 108, 1105\u20131107 (2001).","journal-title":"J. Clin. Invest."},{"key":"264_CR15","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s40495-015-0039-5","volume":"1","author":"NN Yokoyama","year":"2015","unstructured":"Yokoyama, N. N. et al. When anti-aging studies meet cancer chemoprevention: can anti-aging agent kill two birds with one blow? Curr. Pharm. Rep. 1, 420\u2013433 (2015).","journal-title":"Curr. Pharm. Rep."},{"key":"264_CR16","first-page":"565","volume":"24","author":"H Nasri","year":"2014","unstructured":"Nasri, H. & Rafieian-Kopaei, M. Metformin and diabetic kidney disease: a mini-review on recent findings. Iran J. Pediatr. 24, 565\u2013568 (2014).","journal-title":"Iran J. Pediatr."},{"key":"264_CR17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.neulet.2006.10.039","volume":"411","author":"TC Ma","year":"2007","unstructured":"Ma, T. C. et al. Metformin therapy in a transgenic mouse model of Huntington\u2019s disease. Neurosci. Lett. 411, 98\u2013103 (2007).","journal-title":"Neurosci. Lett."},{"key":"264_CR18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0179283","volume":"12","author":"D Herv\u00e1s","year":"2017","unstructured":"Herv\u00e1s, D. et al. Metformin intake associates with better cognitive function in patients with Huntington's disease. PLoS ONE 12, e0179283 (2017).","journal-title":"PLoS ONE"},{"key":"264_CR19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0091-679X(08)61381-3","volume":"48","author":"JA Lewis","year":"1995","unstructured":"Lewis, J. A. & Fleming, J. T. Basic culture methods. Methods Cell Biol. 48, 3\u201329 (1995).","journal-title":"Methods Cell Biol."},{"key":"264_CR20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0091-679X(08)61399-0","volume":"48","author":"C Mello","year":"1995","unstructured":"Mello, C. & Fire, A. DNA transformation. Methods Cell Biol. 48, 451\u2013482 (1995).","journal-title":"Methods Cell Biol."},{"key":"264_CR21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000636","volume":"5","author":"DS Walker","year":"2009","unstructured":"Walker, D. S. et al. Inositol 1,4,5-trisphosphate signalling regulates the avoidance response to nose touch in Caenorhabditis elegans. PLoS Genet. 5, e1000636 (2009).","journal-title":"PLoS Genet."},{"key":"264_CR22","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/ng.248","volume":"40","author":"C Frokjaer-Jensen","year":"2008","unstructured":"Frokjaer-Jensen, C. et al. Single-copy insertion of transgenes in Caenorhabditis elegans. Nat. Genet. 40, 1375\u20131383 (2008).","journal-title":"Nat. Genet."},{"key":"264_CR23","doi-asserted-by":"crossref","first-page":"13318","DOI":"10.1073\/pnas.231476398","volume":"98","author":"JA Parker","year":"2001","unstructured":"Parker, J. A. et al. Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death. Proc. Natl. Acad. Sci. USA 98, 13318\u201313323 (2001).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"264_CR24","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.ygeno.2006.10.007","volume":"89","author":"RP Vazquez-Manrique","year":"2007","unstructured":"Vazquez-Manrique, R. P. et al. The frataxin-encoding operon of Caenorhabditis elegans shows complex structure and regulation. Genomics 89, 392\u2013401 (2007).","journal-title":"Genomics"},{"key":"264_CR25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ygeno.2009.09.001","volume":"95","author":"RP Vazquez-Manrique","year":"2010","unstructured":"Vazquez-Manrique, R. P., Legg, J. C., Olofsson, B., Ly, S. & Baylis, H. A. Improved gene targeting in C. elegans using counter-selection and Flp-mediated marker excision. Genomics 95, 37\u201346 (2010).","journal-title":"Genomics"},{"key":"264_CR26","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","volume":"20","author":"M Foretz","year":"2014","unstructured":"Foretz, M., Guigas, B., Bertrand, L., Pollak, M. & Viollet, B. Metformin: from mechanisms of action to therapies. Cell Metab. 20, 953\u2013966 (2014).","journal-title":"Cell Metab."},{"key":"264_CR27","unstructured":"Can, A. et al. The tail suspension test. J. Vis. Exp. 59, e3769 (2012)."},{"key":"264_CR28","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrn2652","volume":"10","author":"SP Brooks","year":"2009","unstructured":"Brooks, S. P. & Dunnett, S. B. Tests to assess motor phenotype in mice: a user's guide. Nat. Rev. Neurosci. 10, 519\u2013529 (2009).","journal-title":"Nat. Rev. Neurosci."},{"key":"264_CR29","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"264_CR30","first-page":"291","volume":"23","author":"AC Ruifrok","year":"2001","unstructured":"Ruifrok, A. C. & Johnston, D. A. Quantification of histochemical staining by color deconvolution. Anal. Quant. Cytol. Histol. 23, 291\u2013299 (2001).","journal-title":"Anal. Quant. Cytol. Histol."},{"key":"264_CR31","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1177\/0300985813485099","volume":"50","author":"KN Gibson-Corley","year":"2013","unstructured":"Gibson-Corley, K. N., Olivier, A. K. & Meyerholz, D. K. Principles for valid histopathologic scoring in research. Vet. Pathol. 50, 1007\u20131015 (2013).","journal-title":"Vet. Pathol."},{"key":"264_CR32","doi-asserted-by":"crossref","first-page":"10417","DOI":"10.1073\/pnas.152161099","volume":"99","author":"JF Morley","year":"2002","unstructured":"Morley, J. F., Brignull, H. R., Weyers, J. J. & Morimoto, R. I. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 99, 10417\u201310422 (2002).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"264_CR33","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4161\/auto.19496","volume":"8","author":"DJ Klionsky","year":"2012","unstructured":"Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8, 445\u2013544 (2012).","journal-title":"Autophagy"},{"key":"264_CR34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0049838","volume":"7","author":"LB Menalled","year":"2012","unstructured":"Menalled, L. B. et al. Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington\u2019s disease: zQ175. PLoS ONE 7, e49838 (2012).","journal-title":"PLoS ONE"},{"key":"264_CR35","first-page":"348","volume":"17","author":"R Chermat","year":"1986","unstructured":"Chermat, R., Thierry, B., Mico, J. A., Steru, L. & Simon, P. Adaptation of the tail suspension test to the rat. J. Pharm. 17, 348\u2013350 (1986).","journal-title":"J. Pharm."},{"key":"264_CR36","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/0278-5846(87)90002-9","volume":"11","author":"L Steru","year":"1987","unstructured":"Steru, L. et al. The automated Tail Suspension Test: a computerized device which differentiates psychotropic drugs. Prog. Neuropsychopharmacol. Biol. Psychiatry 11, 659\u2013671 (1987).","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"264_CR37","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00428203","volume":"85","author":"L Steru","year":"1985","unstructured":"Steru, L., Chermat, R., Thierry, B. & Simon, P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl.) 85, 367\u2013370 (1985).","journal-title":"Psychopharmacology (Berl.)"},{"key":"264_CR38","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/sj.mp.4001457","volume":"9","author":"JF Cryan","year":"2004","unstructured":"Cryan, J. F. & Mombereau, C. In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol. Psychiatry 9, 326\u2013357 (2004).","journal-title":"Mol. Psychiatry"},{"key":"264_CR39","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S1734-1140(10)70357-1","volume":"62","author":"K Labuzek","year":"2010","unstructured":"Labuzek, K. et al. Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharm. Rep. 62, 956\u2013965 (2010).","journal-title":"Pharm. Rep."},{"key":"264_CR40","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/j.1471-4159.2010.06672.x","volume":"113","author":"I Han","year":"2010","unstructured":"Han, I., You, Y., Kordower, J. H., Brady, S. T. & Morfini, G. A. Differential vulnerability of neurons in Huntington\u2019s disease: the role of cell type-specific features. J. Neurochem. 113, 1073\u20131091 (2010).","journal-title":"J. Neurochem."},{"key":"264_CR41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0092-8674(00)81782-1","volume":"95","author":"F Saudou","year":"1998","unstructured":"Saudou, F., Finkbeiner, S., Devys, D. & Greenberg, M. E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95, 55\u201366 (1998).","journal-title":"Cell"},{"key":"264_CR42","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0006-8993(00)02237-X","volume":"866","author":"I Ferrer","year":"2000","unstructured":"Ferrer, I., Goutan, E., Marin, C., Rey, M. J. & Ribalta, T. Brain-derived neurotrophic factor in Huntington disease. Brain Res. 866, 257\u2013261 (2000).","journal-title":"Brain Res."},{"key":"264_CR43","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1126\/science.1059581","volume":"293","author":"C Zuccato","year":"2001","unstructured":"Zuccato, C. et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 293, 493\u2013498 (2001).","journal-title":"Science"},{"key":"264_CR44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1750-3639.2007.00111.x","volume":"18","author":"C Zuccato","year":"2008","unstructured":"Zuccato, C. et al. Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington's disease. Brain Pathol. 18, 225\u2013238 (2008).","journal-title":"Brain Pathol."},{"key":"264_CR45","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.nbd.2015.08.008","volume":"82","author":"Q Ma","year":"2015","unstructured":"Ma, Q., Yang, J., Li, T., Milner, T. A. & Hempstead, B. L. Selective reduction of striatal mature BDNF without induction of proBDNF in the zQ175 mouse model of Huntington's disease. Neurobiol. Dis. 82, 466\u2013477 (2015).","journal-title":"Neurobiol. Dis."},{"key":"264_CR46","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00041.2009","volume":"90","author":"C Zuccato","year":"2010","unstructured":"Zuccato, C., Valenza, M. & Cattaneo, E. Molecular mechanisms and potential therapeutical targets in Huntington\u2019s disease. Physiol. Rev. 90, 905\u2013981 (2010).","journal-title":"Physiol. Rev."},{"key":"264_CR47","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/glia.23050","volume":"65","author":"AH Jansen","year":"2017","unstructured":"Jansen, A. H. et al. Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific. Glia 65, 50\u201361 (2017).","journal-title":"Glia"},{"key":"264_CR48","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.it.2015.04.007","volume":"36","author":"A Crotti","year":"2015","unstructured":"Crotti, A. & Glass, C. K. The choreography of neuroinflammation in Huntington\u2019s disease. Trends Immunol. 36, 364\u2013373 (2015).","journal-title":"Trends Immunol."},{"key":"264_CR49","volume":"11","author":"Q Peng","year":"2016","unstructured":"Peng, Q. et al. Characterization of behavioral, neuropathological, brain metabolic and key molecular changes in zQ175 knock-in mouse model of Huntington\u2019s disease. PLoS ONE 11, e0148839 (2016).","journal-title":"PLoS ONE"},{"key":"264_CR50","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1006\/bbrc.1996.1112","volume":"224","author":"Y Imai","year":"1996","unstructured":"Imai, Y., Ibata, I., Ito, D., Ohsawa, K. & Kohsaka, S. A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem. Biophys. Res. Commun. 224, 855\u2013862 (1996).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"264_CR51","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/glia.20526","volume":"55","author":"DA Simmons","year":"2007","unstructured":"Simmons, D. A. et al. Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease. Glia 55, 1074\u20131084 (2007).","journal-title":"Glia"},{"key":"264_CR52","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3233\/JHD-140106","volume":"3","author":"KR Bowles","year":"2014","unstructured":"Bowles, K. R. & Jones, L. Kinase signalling in Huntington\u2019s disease. J. Huntingt. Dis. 3, 89\u2013123 (2014).","journal-title":"J. Huntingt. Dis."},{"key":"264_CR53","first-page":"E1","volume":"277","author":"WW Winder","year":"1999","unstructured":"Winder, W. W. & Hardie, D. G. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am. J. Physiol. 277, E1\u2013E10 (1999).","journal-title":"Am. J. Physiol."},{"key":"264_CR54","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1007\/s11095-017-2199-y","volume":"34","author":"M Markowicz-Piasecka","year":"2017","unstructured":"Markowicz-Piasecka, M. et al. Metformin\u2014a Future Therapy For Neurodegenerative Diseases. Pharm. Res. 34, 2614\u20132627 (2017).","journal-title":"Pharm. Res."},{"key":"264_CR55","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0050717","volume":"7","author":"T Heikkinen","year":"2012","unstructured":"Heikkinen, T. et al. Characterization of neurophysiological and behavioral changes, MRI brain volumetry and 1H MRS in zQ175 knock-in mouse model of Huntington's disease. PLoS ONE 7, e50717 (2012).","journal-title":"PLoS ONE"},{"key":"264_CR56","doi-asserted-by":"crossref","first-page":"3654","DOI":"10.1093\/hmg\/ddw212","volume":"25","author":"AL Southwell","year":"2016","unstructured":"Southwell, A. L. et al. An enhanced Q175 knock-in mouse model of Huntington disease with higher mutant huntingtin levels and accelerated disease phenotypes. Hum. Mol. Genet. 25, 3654\u20133675 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"264_CR57","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0123527","volume":"10","author":"N Carty","year":"2015","unstructured":"Carty, N. et al. Characterization of HTT inclusion size, location, and timing in the zQ175 mouse model of Huntington's disease: an in vivo high-content imaging study. PLoS ONE 10, e0123527 (2015).","journal-title":"PLoS ONE"},{"key":"264_CR58","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.38744","volume":"7","author":"I Arnoux","year":"2018","unstructured":"Arnoux, I. et al. Metformin reverses early cortical network dysfunction and behavior changes in Huntington\u2019s disease. Elife 7, e38744 (2018).","journal-title":"Elife"},{"key":"264_CR59","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cmet.2017.10.009","volume":"27","author":"SC Lin","year":"2018","unstructured":"Lin, S. C. & Hardie, D. G. AMPK: sensing glucose as well as cellular energy status. Cell Metab. 27, 299\u2013313 (2018).","journal-title":"Cell Metab."},{"key":"264_CR60","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0064037","volume":"8","author":"C Giampa","year":"2013","unstructured":"Giampa, C. et al. Systemic delivery of recombinant brain derived neurotrophic factor (BDNF) in the R6\/2 mouse model of Huntington\u2019s disease. PLoS ONE 8, e64037 (2013).","journal-title":"PLoS ONE"},{"key":"264_CR61","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","volume":"77","author":"S Brenner","year":"1974","unstructured":"Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71\u201394 (1974).","journal-title":"Genetics"},{"key":"264_CR62","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1101\/gad.1255404","volume":"18","author":"J Apfeld","year":"2004","unstructured":"Apfeld, J., O'Connor, G., McDonagh, T., DiStefano, P. S. & Curtis, R. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev. 18, 3004\u20133009 (2004).","journal-title":"Genes Dev."}],"container-title":["Experimental & Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s12276-019-0264-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s12276-019-0264-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s12276-019-0264-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T04:42:24Z","timestamp":1721364144000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s12276-019-0264-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":62,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["264"],"URL":"https:\/\/doi.org\/10.1038\/s12276-019-0264-9","relation":{},"ISSN":["1226-3613","2092-6413"],"issn-type":[{"value":"1226-3613","type":"print"},{"value":"2092-6413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"5 June 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}