{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:44:53Z","timestamp":1772581493721,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T00:00:00Z","timestamp":1668297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["270949263\/GRK2162"],"award-info":[{"award-number":["270949263\/GRK2162"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["WI 3567\/2-1"],"award-info":[{"award-number":["WI 3567\/2-1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["SCHM 3261\/3-1"],"award-info":[{"award-number":["SCHM 3261\/3-1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["270949263\/GRK2162"],"award-info":[{"award-number":["270949263\/GRK2162"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WI 3567\/2-1"],"award-info":[{"award-number":["WI 3567\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHM 3261\/3-1"],"award-info":[{"award-number":["SCHM 3261\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["270949263\/GRK2162"],"award-info":[{"award-number":["270949263\/GRK2162"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WI 3567\/2-1"],"award-info":[{"award-number":["WI 3567\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHM 3261\/3-1"],"award-info":[{"award-number":["SCHM 3261\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Bundesministerium f\u00fcr Bildung und Forschung (BMBF)","doi-asserted-by":"publisher","award":["270949263\/GRK2162"],"award-info":[{"award-number":["270949263\/GRK2162"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Bundesministerium f\u00fcr Bildung und Forschung (BMBF)","doi-asserted-by":"publisher","award":["WI 3567\/2-1"],"award-info":[{"award-number":["WI 3567\/2-1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Bundesministerium f\u00fcr Bildung und Forschung (BMBF)","doi-asserted-by":"publisher","award":["SCHM 3261\/3-1"],"award-info":[{"award-number":["SCHM 3261\/3-1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Bundesministerium f\u00fcr Bildung und Forschung (BMBF)","doi-asserted-by":"publisher","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tom Wahlig Foundation","award":["270949263\/GRK2162"],"award-info":[{"award-number":["270949263\/GRK2162"]}]},{"name":"Tom Wahlig Foundation","award":["WI 3567\/2-1"],"award-info":[{"award-number":["WI 3567\/2-1"]}]},{"name":"Tom Wahlig Foundation","award":["SCHM 3261\/3-1"],"award-info":[{"award-number":["SCHM 3261\/3-1"]}]},{"name":"Tom Wahlig Foundation","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}]},{"name":"\u201cF\u00f6rderverein f\u00fcr HSP-Forschung\u201d","award":["270949263\/GRK2162"],"award-info":[{"award-number":["270949263\/GRK2162"]}]},{"name":"\u201cF\u00f6rderverein f\u00fcr HSP-Forschung\u201d","award":["WI 3567\/2-1"],"award-info":[{"award-number":["WI 3567\/2-1"]}]},{"name":"\u201cF\u00f6rderverein f\u00fcr HSP-Forschung\u201d","award":["SCHM 3261\/3-1"],"award-info":[{"award-number":["SCHM 3261\/3-1"]}]},{"name":"\u201cF\u00f6rderverein f\u00fcr HSP-Forschung\u201d","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}]},{"name":"\u201cForschungsstiftung Medizin\u201d","award":["270949263\/GRK2162"],"award-info":[{"award-number":["270949263\/GRK2162"]}]},{"name":"\u201cForschungsstiftung Medizin\u201d","award":["WI 3567\/2-1"],"award-info":[{"award-number":["WI 3567\/2-1"]}]},{"name":"\u201cForschungsstiftung Medizin\u201d","award":["SCHM 3261\/3-1"],"award-info":[{"award-number":["SCHM 3261\/3-1"]}]},{"name":"\u201cForschungsstiftung Medizin\u201d","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q\/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11.<\/jats:p>","DOI":"10.3390\/nu14224803","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:21:45Z","timestamp":1668399705000},"page":"4803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-7386","authenticated-orcid":false,"given":"Martin","family":"Regensburger","sequence":"first","affiliation":[{"name":"Division of Molecular Neurology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Division of Stem Cell Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Krumm","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8560-2582","authenticated-orcid":false,"given":"Manuel Alexander","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Neuroradiology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4054-1971","authenticated-orcid":false,"given":"Andreas","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Gie\u00dfen University Hospital, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imke Tabea","family":"Spatz","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique Cornelius","family":"Marterstock","sequence":"additional","affiliation":[{"name":"Institute of Neuroradiology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-8866","authenticated-orcid":false,"given":"Zacharias","family":"Kohl","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnd","family":"Doerfler","sequence":"additional","affiliation":[{"name":"Institute of Neuroradiology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Karrasch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Gie\u00dfen University Hospital, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Winner","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-9204","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Winkler","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/brain\/aww111","article-title":"Genetic and Phenotypic Characterization of Complex Hereditary Spastic Paraplegia","volume":"139","author":"Kara","year":"2016","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/ana.24611","article-title":"Hereditary Spastic Paraplegia: Clinicogenetic Lessons from 608 Patients","volume":"79","author":"Wiethoff","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1093\/brain\/awaa099","article-title":"Janus-Faced Spatacsin (SPG11): Involvement in Neurodevelopment and Multisystem Neurodegeneration","volume":"143","author":"Pozner","year":"2020","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/brain\/awm293","article-title":"Mutations in SPG11 Are Frequent in Autosomal Recessive Spastic Paraplegia with Thin Corpus Callosum, Cognitive Decline and Lower Motor Neuron Degeneration","volume":"131","author":"Stevanin","year":"2008","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1038\/ejhg.2013.27","article-title":"Rapidly Deteriorating Course in Dutch Hereditary Spastic Paraplegia Type 11 Patients","volume":"21","author":"Bot","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116982","DOI":"10.1016\/j.jns.2020.116982","article-title":"Hereditary Spastic Paraplegia Type 11 (SPG11) Is Associated with Obesity and Hypothalamic Damage","volume":"416","author":"Rezende","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00415-016-8254-5","article-title":"Severe Axonal Neuropathy Is a Late Manifestation of SPG11","volume":"263","author":"Manole","year":"2016","journal-title":"J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1001\/archpsyc.1965.01720310065008","article-title":"A Self-Rating Depression Scale","volume":"12","author":"Zung","year":"1965","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/eci.12709","article-title":"CTRP-3 Is Permeable to the Blood-Brain Barrier and Is Not Regulated by Glucose or Lipids in Vivo","volume":"47","author":"Schmid","year":"2017","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/eci.12558","article-title":"Quantification and Regulation of the Adipokines Resistin and Progranulin in Human Cerebrospinal Fluid","volume":"46","author":"Berghoff","year":"2016","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.2215\/CJN.08550814","article-title":"Body Composition and Survival in Dialysis Patients: Results from an International Cohort Study","volume":"10","author":"Marcelli","year":"2015","journal-title":"Clin. J. Am. Soc. Nephro."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000167013","article-title":"Importance of Whole-Body Bioimpedance Spectroscopy for the Management of Fluid Balance","volume":"27","author":"Wabel","year":"2009","journal-title":"Blood Purificat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/ajcn\/85.1.80","article-title":"A Whole-Body Model to Distinguish Excess Fluid from the Hydration of Major Body Tissues","volume":"85","author":"Chamney","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1088\/0967-3334\/27\/9\/012","article-title":"Body Fluid Volume Determination via Body Composition Spectroscopy in Health and Disease","volume":"27","author":"Moissl","year":"2006","journal-title":"Physiol. Meas."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1177\/0884533614568155","article-title":"Bioimpedance at the Bedside","volume":"30","author":"Mulasi","year":"2015","journal-title":"Nutr. Clin. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1093\/ndt\/gfp517","article-title":"Evaluation of Clinical Dry Weight Assessment in Haemodialysis Patients Using Bioimpedance Spectroscopy: A Cross-Sectional Study","volume":"25","author":"Passauer","year":"2010","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tang, X., Oishi, K., Faria, A.V., Hillis, A.E., Albert, M.S., Mori, S., and Miller, M.I. (2013). Bayesian Parameter Estimation and Segmentation in the Multi-Atlas Random Orbit Model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065591"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/459340a","article-title":"Causes and Control of Excess Body Fat","volume":"459","author":"Friedman","year":"2009","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.tem.2013.08.003","article-title":"Progranulin: At the Interface of Neurodegenerative and Metabolic Diseases","volume":"24","author":"Nguyen","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1365-2796.2004.01306.x","article-title":"The Current Biology of Resistin","volume":"255","author":"Steppan","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eaay5947","DOI":"10.1126\/science.aay5947","article-title":"An Atlas of the Protein-Coding Genes in the Human, Pig, and Mouse Brain","volume":"367","author":"Zhong","year":"2020","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"721","DOI":"10.3389\/fpsyg.2013.00721","article-title":"The next Generation of Obesity Treatments: Beyond Suppressing Appetite","volume":"4","author":"Avena","year":"2013","journal-title":"Front. Psychol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1001\/archgenpsychiatry.2010.2","article-title":"Overweight, Obesity, and Depression: A Systematic Review and Meta-Analysis of Longitudinal Studies","volume":"67","author":"Luppino","year":"2010","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1001\/jamaneurol.2015.4756","article-title":"Decline in Weight and Incident Mild Cognitive Impairment: Mayo Clinic Study of Aging","volume":"73","author":"Alhurani","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_25","first-page":"204","article-title":"Obesity in Adults with 22q11.2 Deletion Syndrome","volume":"19","author":"Voll","year":"2017","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.2174\/138920211795677877","article-title":"Prader-Willi Syndrome: Obesity Due to Genomic Imprinting","volume":"12","author":"Butler","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1001\/archneur.61.1.117","article-title":"Clinical Progression and Genetic Analysis in Hereditary Spastic Paraplegia with Thin Corpus Callosum in Spastic Gait Gene 11 (SPG11)","volume":"61","author":"Winner","year":"2004","journal-title":"Arch. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1001\/archneur.63.5.756","article-title":"Hereditary Spastic Paraplegia with Thin Corpus Callosum: Reduction of the SPG11 Interval and Evidence for Further Genetic Heterogeneity","volume":"63","author":"Lossos","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/ajmg.b.30928","article-title":"SPG11 Mutations Cause Kjellin Syndrome, a Hereditary Spastic Paraplegia with Thin Corpus Callosum and Central Retinal Degeneration","volume":"150B","author":"Melberg","year":"2009","journal-title":"Am. J. Med. Genetics. Part B Neuropsychiatr. Genet. Off. Publ. Int. Soc. Psychiatr. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.ophtha.2010.07.024","article-title":"Kjellin Syndrome: Long-Term Neuro-Ophthalmologic Follow-up and Novel Mutations in the SPG11 Gene","volume":"118","author":"Puech","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ymgme.2012.05.020","article-title":"Neurotransmitter Abnormalities and Response to Supplementation in SPG11","volume":"107","author":"Vanderver","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.nicl.2018.05.031","article-title":"SPG11 Mutations Cause Widespread White Matter and Basal Ganglia Abnormalities, but Restricted Cortical Damage","volume":"19","author":"Faber","year":"2018","journal-title":"NeuroImage Clin."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6957","DOI":"10.1073\/pnas.92.15.6957","article-title":"Increased Expression in Adipocytes of Ob RNA in Mice with Lesions of the Hypothalamus and with Mutations at the Db Locus","volume":"92","author":"Maffei","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/32911","article-title":"A Mutation in the Human Leptin Receptor Gene Causes Obesity and Pituitary Dysfunction","volume":"392","author":"Vaisse","year":"1998","journal-title":"Nature"},{"key":"ref_35","first-page":"1723","article-title":"Motor Neuron Degeneration in Spastic Paraplegia 11 Mimics Amyotrophic Lateral Sclerosis Lesions","volume":"139","author":"Denora","year":"2016","journal-title":"Brain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1440-1789.2005.00620.x","article-title":"Autopsy Case of Hereditary Spastic Paraplegia with Thin Corpus Callosum Showing Severe Gliosis in the Cerebral White Matter","volume":"25","author":"Kuru","year":"2005","journal-title":"Neuropathology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/neup.12733","article-title":"Transactivation Response DNA-binding Protein of 43 KDa Proteinopathy and Lysosomal Abnormalities in Spastic Paraplegia Type 11","volume":"41","author":"Mori","year":"2021","journal-title":"Neuropathology"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hayakawa, M., Matsubara, T., Mochizuki, Y., Takeuchi, C., Minamitani, M., Imai, M., Kosaki, K., Arai, T., and Murayama, S. (2022). An Autopsied Case Report of Spastic Paraplegia with Thin Corpus Callosum Carrying a Novel Mutation in the SPG11 Gene: Widespread Degeneration with Eosinophilic Inclusions. BMC Neurol., 22.","DOI":"10.1186\/s12883-021-02514-z"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1002\/mds.27491","article-title":"SPG11-related Parkinsonism: Clinical Profile, Molecular Imaging and L-dopa Response","volume":"33","author":"Faber","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1212\/WNL.51.6.1751","article-title":"Hereditary Spastic Paraplegia with a Thin Corpus Callosum and Thalamic Involvement in Japan","volume":"51","author":"Ueda","year":"1998","journal-title":"Neurology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/brain\/awp325","article-title":"SPATACSIN Mutations Cause Autosomal Recessive Juvenile Amyotrophic Lateral Sclerosis","volume":"133","author":"Orlacchio","year":"2010","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1038\/s41598-017-04706-5","article-title":"Adipokines, C-Reactive Protein and Amyotrophic Lateral Sclerosis\u2014Results from a Population- Based ALS Registry in Germany","volume":"7","author":"Nagel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1136\/jnnp-2017-315795","article-title":"Hypothalamic Atrophy Is Related to Body Mass Index and Age at Onset in Amyotrophic Lateral Sclerosis","volume":"88","author":"Gorges","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1177\/002215549904700309","article-title":"Leptin Receptor Long-Form Splice-Variant Protein Expression in Neuron Cell Bodies of the Brain and Co-Localization with Neuropeptide Y MRNA in the Arcuate Nucleus","volume":"47","author":"Baskin","year":"1999","journal-title":"J. Histochem. Cytochem. Off. J. Histochem. Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000127232","article-title":"Localization of Leptin Receptor in the Human Brain","volume":"66","author":"Couce","year":"1997","journal-title":"Neuroendocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12950","DOI":"10.1074\/jbc.M508691200","article-title":"Leptin Increases Axonal Growth Cone Size in Developing Mouse Cortical Neurons by Convergent Signals Inactivating Glycogen Synthase Kinase-3\u03b2*","volume":"281","author":"Valerio","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/ana.24633","article-title":"GSK3\u00df-dependent Dysregulation of Neurodevelopment in SPG11-patient Induced Pluripotent Stem Cell Model","volume":"79","author":"Mishra","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/hmg\/ddy397","article-title":"Human SPG11 Cerebral Organoids Reveal Cortical Neurogenesis Impairment","volume":"28","author":"Buchsbaum","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"914","DOI":"10.3389\/fnins.2018.00914","article-title":"Tideglusib Rescues Neurite Pathology of SPG11 IPSC Derived Cortical Neurons","volume":"12","author":"Pozner","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1172\/JCI67615","article-title":"Leptin Regulation of Hsp60 Impacts Hypothalamic Insulin Signaling","volume":"123","author":"Kleinridders","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.mcn.2011.04.004","article-title":"Cellular Distribution and Subcellular Localization of Spatacsin and Spastizin, Two Proteins Involved in Hereditary Spastic Paraplegia","volume":"47","author":"Murmu","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"680572","DOI":"10.3389\/fnins.2021.680572","article-title":"Axon-Specific Mitochondrial Pathology in SPG11 Alpha Motor Neurons","volume":"15","author":"Pozner","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1093\/hmg\/ddy156","article-title":"Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias","volume":"27","author":"Denton","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1126\/science.abg7292","article-title":"Caloric Restriction in Humans Reveals Immunometabolic Regulators of Health Span","volume":"375","author":"Spadaro","year":"2022","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbi.2022.09.010","article-title":"Emerging Roles of Leptin in Parkinson\u2019s Disease: Chronic Inflammation, Neuroprotection and More?","volume":"107","author":"Regensburger","year":"2022","journal-title":"Brain Behav. Immun."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/22\/4803\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:17:23Z","timestamp":1760145443000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/22\/4803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,13]]},"references-count":55,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["nu14224803"],"URL":"https:\/\/doi.org\/10.3390\/nu14224803","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,13]]}}}