{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:30:14Z","timestamp":1790695814076,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eye Hope Foundation iVZW, Damme, Belgium (www.eyehopefoundation.org)","award":["VMVBS19195"],"award-info":[{"award-number":["VMVBS19195"]}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PSG471"],"award-info":[{"award-number":["PSG471"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Europe Leuven Strategic Alliance","award":["CELSA\/20\/009"],"award-info":[{"award-number":["CELSA\/20\/009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Wolfram syndrome (WS), also known as a DIDMOAD (diabetes insipidus, early-onset diabetes mellitus, optic nerve atrophy and deafness) is a rare autosomal disorder caused by mutations in the Wolframin1 (WFS1) gene. Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP1 RA) are effective in delaying and restoring blood glucose control in WS animal models and patients. The GLP1 RA liraglutide has also been shown to have neuroprotective properties in aged WS rats. WS is an early-onset, chronic condition. Therefore, early diagnosis and lifelong pharmacological treatment is the best solution to control disease progression. Hence, the aim of this study was to evaluate the efficacy of the long-term liraglutide treatment on the progression of WS symptoms. For this purpose, 2-month-old WS rats were treated with liraglutide up to the age of 18 months and changes in diabetes markers, visual acuity, and hearing sensitivity were monitored over the course of the treatment period. We found that treatment with liraglutide delayed the onset of diabetes and protected against vision loss in a rat model of WS. Therefore, early diagnosis and prophylactic treatment with the liraglutide may also prove to be a promising treatment option for WS patients by increasing the quality of life.<\/jats:p>","DOI":"10.3390\/cells10113193","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T11:32:03Z","timestamp":1637062323000},"page":"3193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Early Intervention and Lifelong Treatment with GLP1 Receptor Agonist Liraglutide in a Wolfram Syndrome Rat Model with an Emphasis on Visual Neurodegeneration, Sensorineural Hearing Loss and Diabetic Phenotype"],"prefix":"10.3390","volume":"10","author":[{"given":"Toomas","family":"Jagom\u00e4e","sequence":"first","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"},{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadri","family":"Seppa","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riin","family":"Reimets","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Pastak","sequence":"additional","affiliation":[{"name":"Eye Clinic of Tartu University Hospital, L. Puusepa 8 Street, 50406 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7004-9174","authenticated-orcid":false,"given":"Mihkel","family":"Plaas","sequence":"additional","affiliation":[{"name":"Ear Clinic of Tartu University Hospital, L. Puusepa 1a Street, 50406 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-8583","authenticated-orcid":false,"given":"Miriam A.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaia Grete","family":"Kukker","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-1411","authenticated-orcid":false,"given":"Lieve","family":"Moons","sequence":"additional","affiliation":[{"name":"Research Group Neural Circuit Development and Regeneration, Department of Biology, Belgium & Leuven Brain Institute, University of Leuven, Naamsestraat 61, Box 2464, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3329-3474","authenticated-orcid":false,"given":"Lies","family":"De Groef","sequence":"additional","affiliation":[{"name":"Research Group Neural Circuit Development and Regeneration, Department of Biology, Belgium & Leuven Brain Institute, University of Leuven, Naamsestraat 61, Box 2464, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-345X","authenticated-orcid":false,"given":"Eero","family":"Vasar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Kaasik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Terasmaa","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Plaas","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 14B Ravila Street, 50411 Tartu, Estonia"},{"name":"Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1136\/jmg.34.10.838","article-title":"Wolfram (DIDMOAD) syndrome","volume":"34","author":"Barrett","year":"1997","journal-title":"J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1016\/S0140-6736(95)92473-6","article-title":"(DIDMOAD) syndrome UK nationwide study of Wolfram","volume":"346","author":"Barrett","year":"1995","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1399-0004.2010.01522.x","article-title":"Wolfram syndrome and WFS1 gene","volume":"79","author":"Rigoli","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1007\/s12020-018-1608-2","article-title":"Natural history and clinical characteristics of 50 patients with Wolfram syndrome","volume":"61","author":"Bueno","year":"2018","journal-title":"Endocrine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/ana.22160","article-title":"Neurologic features and genotype-phenotype correlation in Wolfram syndrome","volume":"69","author":"Chaussenot","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fendo.2018.00018","article-title":"Clinical characteristics of wolfram syndrome in Chinese population and a novel frameshift mutation in WFS1","volume":"9","author":"Duan","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e578","DOI":"10.1212\/NXG.0000000000000578","article-title":"Mild Phenotype of Wolfram Syndrome Associated With a Common Pathogenic Variant Is Predicted by a Structural Model of Wolframin","volume":"7","author":"Shor","year":"2021","journal-title":"Neurol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11892-015-0702-6","article-title":"Wolfram Syndrome: Diagnosis, Management, and Treatment","volume":"16","author":"Urano","year":"2016","journal-title":"Curr. Diab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/hmg\/dds400","article-title":"Vacuolar-type H+-ATPase V1A subunit is a molecular partner of Wolfram syndrome 1 (WFS1) protein, which regulates its expression and stability","volume":"22","author":"Gharanei","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/cne.21777","article-title":"Distribution of Wfs1 protein in the central nervous system of the mouse and its relation to clinical symptoms of the Wolfram syndrome","volume":"509","author":"Luuk","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1093\/hmg\/7.13.2021","article-title":"Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein","volume":"7","author":"Strom","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1097\/WNR.0000000000000624","article-title":"Expression pattern of wolframin, the WFS1 (Wolfram syndrome-1 gene) product, in common marmoset (Callithrix jacchus) cochlea","volume":"27","author":"Suzuki","year":"2016","journal-title":"Neuroreport"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bonnet Wersinger, D., Benkafadar, N., Jagodzinska, J., Hamel, C., Tanizawa, Y., Lenaers, G., and Delettre, C. (2014). Impairment of visual function and retinal ER stress activation in Wfs1-deficient mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097222"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39609","DOI":"10.1074\/jbc.M507426200","article-title":"WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pacreatic \u03b2-cells","volume":"280","author":"Fonseca","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5635","DOI":"10.1016\/j.febslet.2006.09.007","article-title":"WFS1 protein modulates the free Ca2+ concentration in the endoplasmic reticulum","volume":"580","author":"Takei","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cagalinec, M., Liiv, M., Hodurova, Z., Hickey, M.A., Vaarmann, A., Mandel, M., Zeb, A., Choubey, V., Kuum, M., and Safiulina, D. (2016). Role of Mitochondrial Dynamics in Neuronal Development: Mechanism for Wolfram Syndrome. PLoS Biol., 14.","DOI":"10.1371\/journal.pbio.1002511"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/s41419-018-0406-3","article-title":"Wolfram syndrome: MAMs\u2019 connection? Review-article","volume":"9","author":"Delprat","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10220","DOI":"10.1038\/s41598-017-09392-x","article-title":"Wfs1-deficient rats develop primary symptoms of Wolfram syndrome: Insulin-dependent diabetes, optic nerve atrophy and medullary degeneration","volume":"7","author":"Plaas","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15742","DOI":"10.1038\/s41598-019-52295-2","article-title":"GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome","volume":"9","author":"Seppa","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1038\/s41598-021-81768-6","article-title":"Liraglutide, 7,8-DHF and their co-treatment prevents loss of vision and cognitive decline in a Wolfram syndrome rat model","volume":"11","author":"Seppa","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10183","DOI":"10.1038\/s41598-018-28314-z","article-title":"Preventive treatment with liraglutide protects against development of glucose intolerance in a rat model of Wolfram syndrome","volume":"8","author":"Toots","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2174\/1573399815666190502114924","article-title":"GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus","volume":"16","author":"Dahiya","year":"2020","journal-title":"Curr. Diabetes Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cmet.2006.10.001","article-title":"GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress","volume":"4","author":"Yusta","year":"2006","journal-title":"Cell Metab."},{"key":"ref_24","first-page":"7","article-title":"Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome","volume":"1","author":"Sedman","year":"2016","journal-title":"J. Diabetes."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1007\/s00125-018-4679-y","article-title":"Activation of GLP-1 receptor signalling alleviates cellular stresses and improves beta cell function in a mouse model of Wolfram syndrome","volume":"61","author":"Kondo","year":"2018","journal-title":"Diabetologia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1159\/000510852","article-title":"Efficacy of GLP-1 Agonist Therapy in Autosomal Dominant WFS1-Related Disorder: A Case Report","volume":"93","author":"Scully","year":"2021","journal-title":"Horm. Res. Paediatr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Luippold, G., Bedenik, J., Voigt, A., and Grempler, R. (2016). Short-and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156346"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1017\/S175173110800387X","article-title":"Improvement of insulin response in the streptozotocin model of insulin-dependent diabetes mellitus. Insulin response with and without a long-acting insulin treatment","volume":"3","author":"Nordquist","year":"2009","journal-title":"Animal"},{"key":"ref_29","first-page":"327","article-title":"Spontaneous Neoplasms in Aged Sprague-Dawley Rats","volume":"20","author":"Chandra","year":"1992","journal-title":"Arch. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1121\/1.382104","article-title":"Stimulated acoustic emissions from within the human auditory system","volume":"64","author":"Kemp","year":"1978","journal-title":"J. Acoust Soc. Am."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/bmb\/63.1.223","article-title":"Otoacoustic emissions, their origin in cochlear function, and use","volume":"63","author":"Kemp","year":"2002","journal-title":"Br. Med. Bull."},{"key":"ref_32","unstructured":"(2021, October 06). Pathme GmbH Whitepaper. Available online: https:\/\/www.pathme.de\/download\/whitepapers\/Whitepaper_Short_RelationBetweenDPOAEs_and_behavioural_pure_tone_threshold.pdf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.joto.2018.03.002","article-title":"Isoflurane anesthesia suppresses distortion product otoacoustic emissions in rats","volume":"13","author":"Sheppard","year":"2018","journal-title":"J. Otol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2307\/3579097","article-title":"Inhibition of Radiation Cataractogenesis by WR-77913","volume":"141","author":"Livesey","year":"2014","journal-title":"Radiat. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1167\/iovs.08-3267","article-title":"Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in na\u00efve and optic nerve-injured retinas","volume":"50","author":"Agudo","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.exer.2016.04.010","article-title":"A freely available semi-automated method for quantifying retinal ganglion cells in entire retinal flatmounts","volume":"147","author":"Geeraerts","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji\u2014An Open platform for biological image analysis","volume":"9","author":"Schindelin","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_38","first-page":"75","article-title":"Four cases of Wolfram syndrome: Ophthalmologic findings and complications","volume":"252","author":"Seynaeve","year":"1994","journal-title":"Bull. Soc. Belge Ophtalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/gim.2012.180","article-title":"Genotypic classification of patients with Wolfram syndrome: Insights into the natural history of the disease and correlation with phenotype","volume":"15","author":"Nunes","year":"2013","journal-title":"Genet. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fendo.2019.00155","article-title":"The Discovery and Development of Liraglutide and Semaglutide","volume":"10","author":"Knudsen","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_41","first-page":"1986","article-title":"Localization and distribution of wolframin in human tissues","volume":"4","author":"Manente","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"173443","DOI":"10.1016\/j.ejphar.2020.173443","article-title":"Tolerance develops toward GLP-1 receptor agonists\u2019 glucose-lowering effect in mice","volume":"885","author":"Sedman","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1538\/expanim.14-0084","article-title":"Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: Effects of SGLT inhibitor phlorizin","volume":"64","author":"Katsuda","year":"2015","journal-title":"Exp. Anim."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.2337\/diabetes.53.5.1187","article-title":"One Week\u2019s Treatment with the Long-Acting Glucose Release in Patients with Type 2 Diabetes","volume":"53","author":"Degn","year":"2004","journal-title":"Diabetes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.2337\/diacare.27.8.1915","article-title":"The Effect of Liraglutide, a Long-Acting 24-h Energy Expenditure in Patients Glycemic Control, Body Composition, and Glucagon-Like Peptide 1 Derivative, on with Type 2 Diabetes","volume":"27","author":"Harder","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13023-018-0852-0","article-title":"Longitudinal hearing loss in Wolfram syndrome","volume":"13","author":"Karzon","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_47","first-page":"281","article-title":"Distortion product otoacoustic emissions: A tool for hearing assessment and scientific study","volume":"103","author":"Abdala","year":"2001","journal-title":"Volta Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1136\/jmg.2005.034892","article-title":"Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene","volume":"43","author":"Eiberg","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jcg.2011.01.001","article-title":"Identification of two novel missense WFS1 mutations, H696Y and R703H, in patients with non-syndromic low-frequency sensorineural hearing loss","volume":"38","author":"Sun","year":"2011","journal-title":"J. Genet. Genom."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1001\/archotol.129.4.411","article-title":"Mutations in the Wolfram syndrome type 1 gene (WFS1) define a clinical entity of dominant low-frequency sensorineural hearing loss","volume":"129","author":"Lesperance","year":"2003","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.1121\/1.5132553","article-title":"The rat animal model for noise-induced hearing loss","volume":"146","author":"Escabi","year":"2019","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00401-009-0546-8","article-title":"Wolfram syndrome: A clinicopathologic correlation","volume":"118","author":"Hilson","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jaapos.2014.07.162","article-title":"Ophthalmologic correlates of disease severity in children and adolescents with Wolfram syndrome","volume":"18","author":"Hoekel","year":"2014","journal-title":"J. Am. Assoc. Pediatric Ophthalmol. Strabismus"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s004010050635","article-title":"Wolfram syndrome: A neuropathological study","volume":"93","author":"Molins","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/dmcn.14040","article-title":"Optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram syndrome","volume":"61","author":"Zmyslowska","year":"2019","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.3174\/ajnr.A6831","article-title":"Longitudinal assessment of neuroradiologic features in wolfram syndrome","volume":"41","author":"Samara","year":"2020","journal-title":"Am. J. Neuroradiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.visres.2004.12.015","article-title":"The optomotor response: A robust first-line visual screening method for mice","volume":"45","author":"Pierre","year":"2005","journal-title":"Vis. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1159\/000265463","article-title":"Effects of diabetes and insulin treatment on sorbitol and water of rat lenses","volume":"18","author":"Coulter","year":"1986","journal-title":"Ophthalmic Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ejphar.2008.03.025","article-title":"GLP-1 agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by beta-amyloid","volume":"587","author":"Gault","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.expneurol.2006.09.028","article-title":"Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy","volume":"203","author":"Perry","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/0271678X20952011","article-title":"Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: A systematic scoping review","volume":"41","author":"Maskery","year":"2021","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"871","DOI":"10.2165\/11635890-000000000-00000","article-title":"Potential Role of Glucagon-Like Peptide-1 (GLP-1) in Neuroprotection","volume":"26","year":"2012","journal-title":"CNS Drugs"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:31:10Z","timestamp":1760167870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":62,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cells10113193"],"URL":"https:\/\/doi.org\/10.3390\/cells10113193","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-903256\/v1","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,16]]}}}