{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:22:55Z","timestamp":1792264975630,"version":"4.4.0"},"reference-count":124,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Convocatoria de Subvenciones para la Financiaci\u00f3n de la Investigaci\u00f3n y la Innovaci\u00f3n Biom\u00e9dica y en Ciencias de la Salud en el Marco de la Iniciativa Territorial Integrada 2014-2020 para la Provincia de C\u00e1diz, Fondos ITI-FEDER","award":["PI-0012-2019"],"award-info":[{"award-number":["PI-0012-2019"]}]},{"name":"Convocatoria de Subvenciones para la Financiaci\u00f3n de la Investigaci\u00f3n y la Innovaci\u00f3n Biom\u00e9dica y en Ciencias de la Salud en el Marco de la Iniciativa Territorial Integrada 2014-2020 para la Provincia de C\u00e1diz, Fondos ITI-FEDER","award":["PI-0036-2020"],"award-info":[{"award-number":["PI-0036-2020"]}]},{"name":"Consejer\u00eda de Salud de la Junta de Andaluc\u00eda","award":["PI-0012-2019"],"award-info":[{"award-number":["PI-0012-2019"]}]},{"name":"Consejer\u00eda de Salud de la Junta de Andaluc\u00eda","award":["PI-0036-2020"],"award-info":[{"award-number":["PI-0036-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a neurodegenerative disorder caused by a toxic, aggregation-prone expansion of CAG repeats in the HTT gene with an age-dependent progression that leads to behavioral, cognitive and motor symptoms. Principally affecting the frontal cortex and the striatum, mHTT disrupts many cellular functions. In fact, increasing evidence shows that peripheral tissues are affected by neurodegenerative diseases. It establishes an active crosstalk between peripheral tissues and the brain in different neurodegenerative diseases. This review focuses on the current knowledge of peripheral tissue effects in HD animal and cell experimental models and identifies biomarkers and mechanisms involved or affected in the progression of the disease as new therapeutic or early diagnostic options. The particular changes in serum\/plasma, blood cells such as lymphocytes, immune blood cells, the pancreas, the heart, the retina, the liver, the kidney and pericytes as a part of the blood\u2013brain barrier are described. It is important to note that several changes in different mouse models of HD present differences between them and between the different ages analyzed. The understanding of the impact of peripheral organ inflammation in HD may open new avenues for the development of novel therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms23116089","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:50:51Z","timestamp":1653814251000},"page":"6089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A New Perspective on Huntington\u2019s Disease: How a Neurological Disorder Influences the Peripheral Tissues"],"prefix":"10.3390","volume":"23","author":[{"given":"Laura","family":"G\u00f3mez-Jaramillo","sequence":"first","affiliation":[{"name":"Undad de Investigaci\u00f3n, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Ciencias Biom\u00e9dicas de la Provincia de C\u00e1diz (INiBICA), 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-0812","authenticated-orcid":false,"given":"F\u00e1tima","family":"Cano-Cano","sequence":"additional","affiliation":[{"name":"Undad de Investigaci\u00f3n, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Ciencias Biom\u00e9dicas de la Provincia de C\u00e1diz (INiBICA), 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2332-6153","authenticated-orcid":false,"given":"Mar\u00eda del Carmen","family":"Gonz\u00e1lez-Montelongo","sequence":"additional","affiliation":[{"name":"Undad de Investigaci\u00f3n, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Ciencias Biom\u00e9dicas de la Provincia de C\u00e1diz (INiBICA), 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-2153","authenticated-orcid":false,"given":"Antonio","family":"Campos-Caro","sequence":"additional","affiliation":[{"name":"Undad de Investigaci\u00f3n, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Ciencias Biom\u00e9dicas de la Provincia de C\u00e1diz (INiBICA), 11002 C\u00e1diz, Spain"},{"name":"\u00c1rea de Gen\u00e9tica, Departamento de Biomedicina, Biotecnolog\u00eda y Salud P\u00fablica, Universidad de C\u00e1diz, 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Aguilar-Diosdado","sequence":"additional","affiliation":[{"name":"Undad de Investigaci\u00f3n, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Ciencias Biom\u00e9dicas de la Provincia de C\u00e1diz (INiBICA), 11002 C\u00e1diz, Spain"},{"name":"Departamento de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Puerta del Mar, Universidad de C\u00e1diz, 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5136-1725","authenticated-orcid":false,"given":"Ana I.","family":"Arroba","sequence":"additional","affiliation":[{"name":"Undad de Investigaci\u00f3n, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Ciencias Biom\u00e9dicas de la Provincia de C\u00e1diz (INiBICA), 11002 C\u00e1diz, Spain"},{"name":"\u00c1rea de Gen\u00e9tica, Departamento de Biomedicina, Biotecnolog\u00eda y Salud P\u00fablica, Universidad de C\u00e1diz, 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13024-018-0284-2","article-title":"Peripheral immune system in aging and Alzheimer\u2019s disease","volume":"13","author":"Cao","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/mds.26605","article-title":"Neuropathological Basis of Nonmotor Manifestations of Parkinson\u2019s Disease","volume":"31","author":"Adler","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1007\/s12035-018-1151-4","article-title":"Peripheral Biomarkers for Early Detection of Alzheimer\u2019s and Parkinson\u2019s Diseases","volume":"56","author":"Htike","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Giaccone, G., and Moda, F. (2020). Pmca applications for prion detection in peripheral tissues of patients with variant creutzfeldt-jakob disease. Biomolecules, 10.","DOI":"10.3390\/biom10030405"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0378-1119(98)00342-4","article-title":"Characterization of the Huntington\u2019s disease (HD) gene homolog in the zebrafish Danio rerio","volume":"217","author":"Karlovich","year":"1998","journal-title":"Gene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/ana.410310412","article-title":"Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington\u2019s disease","volume":"31","author":"Albin","year":"1992","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000212174","article-title":"Abnormal glucose tolerance and arginine tolerance tests in Huntington\u2019s disease","volume":"23","author":"Podolsky","year":"1977","journal-title":"Gerontology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.5694\/j.1326-5377.1981.tb135681.x","article-title":"Body weight and dietary factors in Huntington\u2019s Disease patients compared with matched controls","volume":"1","author":"Sanberg","year":"1981","journal-title":"Med. J. Aust."},{"key":"ref_10","unstructured":"Cells, R.E.D., Huntington, F., Zanella, A., Izzo, C., Meola, G., Colotti, M.T., Silani, V., Pellegata, G., and Scarlato, G. (1980). Experimental procedures Haematological investigations. Blood, 93\u2013103."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1136\/jmg.19.3.168","article-title":"Sensitivity to ionising radiation of lymphocytes from Huntington\u2019s chorea patients compared to controls","volume":"19","author":"Mcgovern","year":"1982","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/BF00286586","article-title":"The current state of research with peripheral tissues in Huntington disease","volume":"66","author":"Beverstock","year":"1984","journal-title":"Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1523\/JNEUROSCI.4846-11.2012","article-title":"Neurobiology of Disease Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington\u2019s Disease","volume":"32","author":"Kwan","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"541259","DOI":"10.1155\/2013\/541259","article-title":"The Role of the Immune System in Huntington\u2019s Disease","volume":"2013","author":"Ellrichmann","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1006\/nbdi.2002.0562","article-title":"Huntington\u2019s disease of the endocrine pancreas: Insulin deficiency and diabetes mellitus due to impaired insulin gene expression","volume":"11","author":"Andreassen","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3233\/JHD-2012-120004","article-title":"Direct Evidence of Progressive Cardiac Dysfunction in a Transgenic Mouse Model of Huntington\u2019s Disease","volume":"1","author":"Wood","year":"2012","journal-title":"J. Huntingt. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e968003","DOI":"10.4161\/2167549X.2014.968003","article-title":"Drosophila as a potential model to ameliorate mutant Huntington-mediated cardiac amyloidosis","volume":"2","author":"Trujillo","year":"2014","journal-title":"Rare Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1093\/hmg\/11.26.3351","article-title":"Progressive retinal degeneration and dysfunction in R6 Huntington\u2019s disease mice","volume":"11","author":"Helmlinger","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/mds.25862","article-title":"Progressive hepatic mitochondrial dysfunction in premanifest Huntington\u2019s disease","volume":"29","author":"Hoffmann","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101358","DOI":"10.1016\/j.arr.2021.101358","article-title":"Systemic manifestation and contribution of peripheral tissues to Huntington\u2019s disease pathogenesis","volume":"69","author":"Chuang","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5441","DOI":"10.1038\/s41380-020-0787-4","article-title":"Shedding a new light on Huntington\u2019s disease: How blood can both propagate and ameliorate disease pathology","volume":"26","author":"Rieux","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1474-4422(09)70178-4","article-title":"Beyond the brain: Widespread pathology in Huntington\u2019s disease","volume":"8","author":"Brundin","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.tibs.2006.06.009","article-title":"Huntington\u2019s disease: Seeing the pathogenic process through a genetic lens","volume":"31","author":"Gusella","year":"2006","journal-title":"Trends Biochem. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/sj.embor.7400250","article-title":"Huntingtin and the molecular pathogenesis of Huntington\u2019s disease: Fourth in molecular medicine review series","volume":"5","author":"Landles","year":"2004","journal-title":"EMBO Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.neuron.2006.09.025","article-title":"Drosophila in the Study of Neurodegenerative Disease","volume":"52","author":"Marsh","year":"2006","journal-title":"Neuron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD Gene with an Expanded","volume":"87","author":"Mangiarini","year":"1996","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/hmg\/8.3.397","article-title":"Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin","volume":"8","author":"Schilling","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/bpa.12191","article-title":"The Differential Profiling of Ubiquitin-Proteasome and Autophagy Systems in Different Tissues before the Onset of Huntington\u2019s Disease Models","volume":"25","author":"Her","year":"2015","journal-title":"Brain Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6182","DOI":"10.1523\/JNEUROSCI.0857-08.2008","article-title":"Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice","volume":"28","author":"Gray","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1093\/hmg\/ddg169","article-title":"Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease","volume":"12","author":"Slow","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Menalled, L.B., Kudwa, A.E., Miller, S., Fitzpatrick, J., Watson-Johnson, J., Keating, N., Ruiz, M., Mushlin, R., Alosio, W., and McConnell, K. (2012). Comprehensive Behavioral and Molecular Characterization of a New Knock-In Mouse Model of Huntington\u2019s Disease: ZQ175. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049838"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0896-6273(00)80764-3","article-title":"A YAC mouse model for Huntington\u2019s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration","volume":"23","author":"Hodgson","year":"1999","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/ng1297-404","article-title":"Huntingtin is required for neurogenesis and is not impaired by the Huntington\u2019s disease CAG expansion","volume":"17","author":"White","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/hmg\/10.2.137","article-title":"Neurological abnormalities in a knock-in mouse model of Huntington\u2019s disease","volume":"10","author":"Lin","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rocha, N.P., Ribeiro, F.M., Furr-Stimming, E., and Teixeira, A.L. (2016). Neuroimmunology of Huntington\u2019s Disease: Revisiting Evidencefrom Human Studies. Mediat. Inflamm., 1\u201310.","DOI":"10.1155\/2016\/8653132"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.nbd.2009.05.007","article-title":"Systematic behavioral evaluation of Huntington\u2019s disease transgenic and knock-in mouse models","volume":"35","author":"Menalled","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"116653","DOI":"10.1016\/j.lfs.2019.116653","article-title":"Inflammatory changes in peripheral organs in the BACHD murine model of Huntington\u2019s disease","volume":"232","author":"Vieira","year":"2019","journal-title":"Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11447","DOI":"10.1038\/s41598-018-29792-x","article-title":"In vivo neutralization of the protagonist role of macrophages during the chronic inflammatory stage of Huntington\u2019s disease","volume":"8","author":"Andre","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1084\/jem.20080178","article-title":"A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington\u2019s disease","volume":"205","author":"Wild","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3233\/JHD-140116","article-title":"Novel BAC mouse model of Huntington\u2019s disease with 225 CAG repeats exhibits an early widespread and stable degenerative phenotype","volume":"4","author":"Wegrzynowicz","year":"2015","journal-title":"J. Huntingt. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fimmu.2018.00298","article-title":"The Potential Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders","volume":"9","author":"Arts","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.immuni.2016.02.024","article-title":"Tissue-Resident Macrophage Ontogeny and Homeostasis","volume":"44","author":"Ginhoux","year":"2016","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Novellino, F., Sacc\u00e0, V., Donato, A., Zaffino, P., Spadea, M.F., Vismara, M., Arcidiacono, B., Malara, N., Presta, I., and Donato, G. (2020). Molecular Sciences Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031115"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17269","DOI":"10.1038\/s41598-020-74042-8","article-title":"Wild-type huntingtin regulates human macrophage function","volume":"10","author":"Farag","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.3389\/fimmu.2019.02405","article-title":"Expression of Human Mutant Huntingtin Protein in Drosophila Hemocytes Impairs Immune Responses","volume":"10","author":"Valanne","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.expneurol.2009.05.012","article-title":"Huntington\u2019s disease: The current state of research with peripheral tissues","volume":"219","author":"Sassone","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.immuni.2018.04.025","article-title":"Hemogenic Endothelial Fate Mapping Reveals Dual Developmental Origin of Mast Cells","volume":"48","author":"Gentek","year":"2018","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/intimm\/dxp011","article-title":"T-cell responses to neurofilament light protein are part of the normal immune repertoire","volume":"21","author":"Huizinga","year":"2009","journal-title":"Int. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/S0140-6736(00)02239-X","article-title":"Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma","volume":"355","author":"Gereda","year":"2000","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.nbd.2014.10.012","article-title":"Characterisation of immune cell function in fragment and full-length Huntington\u2019s disease mouse models","volume":"73","author":"Andre","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6186","DOI":"10.1093\/hmg\/ddv335","article-title":"Transcriptional dysregulation of inflammatory\/immune pathways after active vaccination against Huntington\u2032s disease","volume":"24","author":"Ramsingh","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0092-8674(01)00449-4","article-title":"Dendritic Cells: Specialized and Regulated Antigen Processing Machines","volume":"106","author":"Mellman","year":"2001","journal-title":"Cell."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1126\/science.1170540","article-title":"In vivo analysis of dendritic cell development and homeostasis","volume":"324","author":"Liu","year":"2010","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"563784","DOI":"10.1155\/2011\/563784","article-title":"Huntington\u2019s disease: An immune perspective","volume":"2011","author":"Nayak","year":"2011","journal-title":"Neurol. Res. Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1084\/jem.191.2.365","article-title":"Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand","volume":"191","author":"Murata","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/hmg\/8.5.813","article-title":"Formation of polyglutamine inclusions in non-CNS tissue","volume":"8","author":"Sathasivam","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Moffitt, H., McPhail, G.D., Woodman, B., Hobbs, C., and Bates, G.P. (2009). Formation of Polyglutamine Inclusions in a Wide Range of Non-CNS Tissues in the HdhQ150 Knock-In Mouse Model of Huntington\u2019s Disease. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008025"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8411","DOI":"10.1523\/JNEUROSCI.0775-14.2014","article-title":"Ubiquitin-activating enzyme activity contributes to differential accumulation of mutant huntingtin in brain and peripheral tissues","volume":"34","author":"Wade","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1093\/hmg\/ddl072","article-title":"Body weight is modulated by levels of full-length Huntingtin","volume":"15","author":"Gibson","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1093\/hmg\/ddv209","article-title":"Oxidative metabolism in YAC128 mouse model of Huntington\u2019s disease","volume":"24","author":"Hamilton","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1179\/1743132812Y.0000000073","article-title":"Oxidative stress and inflammation biomarkers in the blood of patients with huntington\u2019s disease","volume":"34","author":"Tasset","year":"2012","journal-title":"Neurol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fphar.2017.00370","article-title":"Indoxyl sulfate affects glial function increasing oxidative stress and neuroinflammation in chronic kidney disease: Interaction between astrocytes and microglia","volume":"8","author":"Adesso","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nrneph.2017.52","article-title":"The systemic nature of CKD","volume":"13","author":"Zoccali","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Stanciu, G.D., Ababei, D.C., Bild, V., Bild, W., Paduraru, L., Gutu, M.M., and Tamba, B.I. (2020). Renal contributions in the pathophysiology and neuropathological substrates shared by chronic kidney disease and Alzheimer\u2019s disease. Brain Sci., 10.","DOI":"10.3390\/brainsci10080563"},{"key":"ref_66","first-page":"206","article-title":"Cross-talks between the kidneys and the central nervous system in multiple sclerosis","volume":"9","author":"Rostami","year":"2018","journal-title":"Casp. J. Intern. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3389\/fimmu.2017.00405","article-title":"Interleukin-6 signaling pathway and its role in kidney disease: An update","volume":"8","author":"Su","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/nature05291","article-title":"The roles of intracellular protein-degradation pathways in neurodegeneration","volume":"443","author":"Rubinsztein","year":"2006","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ng1362","article-title":"Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease","volume":"36","author":"Ravikumar","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1111\/j.1742-4658.2008.06562.x","article-title":"Huntington\u2019s disease: Degradation of mutant huntingtin by autophagy","volume":"275","author":"Sarkar","year":"2008","journal-title":"FEBS J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/jnc.12647","article-title":"Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington\u2019s disease","volume":"129","author":"Liu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_72","first-page":"151","article-title":"Huntington\u2019s chorea: A study of liver function and histology","volume":"42","author":"Bolt","year":"1973","journal-title":"Q. J. Med."},{"key":"ref_73","unstructured":"Warren, S.T., and Wells, R.T. (1998). Huntington\u2019s disease. Genetic Instabilities and Hereditary Neurological Diseases, Academic Press."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnmol.2014.00077","article-title":"Ubiquitin-proteasome system involvement in Huntington\u2019s disease","volume":"7","author":"Ortega","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/hmg\/ddl481","article-title":"Dysregulation of C\/EBP\u03b1 by mutant Huntingtin causes the urea cycle deficiency in Huntington\u2019s disease","volume":"16","author":"Chiang","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.bbadis.2011.05.006","article-title":"The dysfunction of hepatic transcriptional factors in mice with Huntington\u2019s Disease","volume":"1812","author":"Chiang","year":"2011","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1093\/hmg\/ddq229","article-title":"Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington\u2019s disease following chronic energy deprivation","volume":"19","author":"Chaturvedi","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.nbd.2010.08.009","article-title":"Reduced gluconeogenesis and lactate clearance in Huntington\u2019s disease","volume":"40","author":"Josefsen","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0166-2236(93)90117-5","article-title":"Do defecs in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases?","volume":"16","author":"Beal","year":"1993","journal-title":"Trends Neurosci."},{"key":"ref_80","first-page":"199","article-title":"Local cerebral glucose utilization in symptomatic and presymptomatic Huntington\u2019s disease","volume":"63","author":"Kuhl","year":"1985","journal-title":"Res. Publ. Assoc. Res. Nerv. Ment. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1111\/j.1471-4159.1985.tb07192.x","article-title":"Regional Mitochondrial Respiratory Activity in Huntington\u2019s Disease Brain","volume":"44","author":"Brennan","year":"1985","journal-title":"J. Neurochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/ana.410410514","article-title":"Oxidative damage and metabolic dysfunction in Huntington\u2019s disease: Selective vulnerability of the basal ganglia","volume":"41","author":"Browne","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1093\/hmg\/ddh162","article-title":"Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release","volume":"13","author":"Choo","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8989","DOI":"10.1523\/JNEUROSCI.1830-07.2007","article-title":"Longitudinal Evaluation of the Hdh (CAG)150 Knock-In Murine Model of Huntington\u2019s Disease","volume":"27","author":"Heng","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Young, D., Mayer, F., Vidotto, N., Schweizer, T., Berth, R., Abramowski, D., Shimshek, D.R., van der Putten, P.H., and Schmid, P. (2013). Mutant Huntingtin Gene-Dose Impacts on Aggregate Deposition, DARPP32 Expression and Neuroinflammation in HdhQ150 Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075108"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/cne.20327","article-title":"Fine-structural analysis and connexin expression in the retina of a transgenic model of Huntington\u2019s disease","volume":"479","author":"Habbes","year":"2004","journal-title":"J. Comp. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S0896-6273(00)80573-5","article-title":"Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons","volume":"21","author":"Jackson","year":"1998","journal-title":"Neuron"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00401-005-1092-7","article-title":"Is the retina affected in Huntington disease?","volume":"110","author":"Saft","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.nbd.2015.05.008","article-title":"A novel function of Huntingtin in the cilium and retinal ciliopathy in Huntington\u2019s disease mice","volume":"80","author":"Karam","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/ana.22598","article-title":"Loss of junctophilin-3 contributes to huntington disease-like 2 pathogenesis","volume":"71","author":"Seixas","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10811","DOI":"10.1073\/pnas.0509863103","article-title":"Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins","volume":"103","author":"Moriguchi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1006\/bbrc.2002.6649","article-title":"Motor discoordination in mutant mice lacking junctophilin type 3","volume":"292","author":"Nishi","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.nbd.2011.12.004","article-title":"Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6\/1 mouse model of Huntington\u2019s disease","volume":"45","author":"Batcha","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Ragauskas, S., Leinonen, H., Puranen, J., R\u00f6 Nkk\u00f6, S., Nymark, S., Gurevicius, K., Lipponen, A., Kontkanen, O., Puoliv\u00e4li, J., and Tanila, H. (2014). Early Retinal Function Deficit without Prominent Morphological Changes in the R6\/2 Mouse Model of Huntington\u2019s Disease. PloS ONE, 9.","DOI":"10.1371\/journal.pone.0113317"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/S0140-6736(13)60023-9","article-title":"Interleukin-1 antagonism in type 1 diabetes of recent onset: Two multicentre, randomised, double-blind, placebo-controlled trials","volume":"381","author":"Moran","year":"2013","journal-title":"Lancet"},{"key":"ref_96","first-page":"5418","article-title":"Attenuated pupillary light responses and downregulation of opsin expression parallel decline in circadian disruption in two different mouse models of Huntington\u2019s disease","volume":"25","author":"Ouk","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1523\/JNEUROSCI.0571-18.2018","article-title":"Degeneration of ipRGCs in mouse models of Huntington\u2019s disease disrupts non-image-forming behaviors before motor impairment","volume":"39","author":"Lin","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/j.1471-4159.2009.06363.x","article-title":"BAG1 modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution","volume":"111","author":"Sroka","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/cddis.2013.351","article-title":"Suppression of polyglutamine protein toxicity by co-expression of a heat-shock protein 40 and a heat-shock protein 110","volume":"4","author":"Kuo","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1126\/science.1067262","article-title":"Phototransduction by retinal ganglion cells that set the circadian clock","volume":"295","author":"Berson","year":"2002","journal-title":"Science"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1126\/science.1077293","article-title":"Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice","volume":"299","author":"Lucas","year":"2003","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature06829","article-title":"Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision","volume":"453","author":"Ecker","year":"2008","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1523\/JNEUROSCI.3842-04.2005","article-title":"Disintegration of the sleep-wake cycle and circadian timing in Huntington\u2019s disease","volume":"25","author":"Morton","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7869","DOI":"10.1523\/JNEUROSCI.0649-07.2007","article-title":"Pharmacological imposition of sleep slows cognitive decline and reverses dysregulation of circadian gene expression in a transgenic mouse model of Huntington\u2019s disease","volume":"27","author":"Pallier","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.expneurol.2010.12.011","article-title":"Dysfunctions in circadian behavior and physiology in mouse models of Huntington\u2019s disease","volume":"228","author":"Kudo","year":"2011","journal-title":"Exp. Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1399-0004.1985.tb00185.x","article-title":"Diabetes mellitus in Huntington disease","volume":"27","author":"Farrer","year":"1985","journal-title":"Clin. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1365-2826.2007.01629.x","article-title":"Impaired glucose tolerance in the R6\/1 transgenic mouse model of Huntington\u2019s disease","volume":"20","author":"Josefsen","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/hmg\/ddi053","article-title":"The R6\/2 transgenic mouse model of Huntington\u2019s disease develops diabetes due to deficient b-cell mass and exocytosis","volume":"14","author":"Fex","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/hmg\/10.2.145","article-title":"Abnormalities in the functioning of adipocytes from R6\/2 mice that are transgenic for the Huntington\u2019s disease mutation","volume":"10","author":"Fain","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1046\/j.1471-4159.2000.0742108.x","article-title":"Nonlinear Decrease over Time in N-Acetyl Aspartate Levels in the Absence of Neuronal Loss and Increases in Glutamine and Glucose in Transgenic Huntington\u2019s Disease Mice","volume":"74","author":"Jenkins","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"318","DOI":"10.2337\/db08-0799","article-title":"Exendin-4 Improves Glycemic Control, Ameliorates Brain and Pancreatic Pathologies, and Extends Survival in a Mouse Model of Huntington\u2019s Disease","volume":"58","author":"Martin","year":"2009","journal-title":"Diabetes"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Lopes, C., Duarte, A.I., Hayden, M., and Rego, A.C. (2012, January 23\u201325). Peripheral and cerebral metabolic features in an animal model of Huntington\u2019s disease. Proceedings of the 2012 IEEE 2nd Portuguese Meeting in Bioengineering (ENBENG), Coimbra, Portugal.","DOI":"10.1109\/ENBENG.2012.6331390"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/ana.410200305","article-title":"PET scan investigations of Huntington\u2019s disease: Cerebral metabolic correlates of neurological features and functional decline","volume":"20","author":"Young","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2337\/diabetes.48.3.649","article-title":"Mice transgenic for an expanded CAG repeat in the Huntington\u2019s disease gene develop diabetes","volume":"48","author":"Hurlbert","year":"1999","journal-title":"Diabetes"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1523\/JNEUROSCI.19-08-03248.1999","article-title":"Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington\u2019s Disease Mutation","volume":"19","author":"Carter","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/j.1365-2826.2009.01898.x","article-title":"Huntington\u2019s disease does not appear to increase the risk of diabetes mellitus","volume":"21","author":"Boesgaard","year":"2009","journal-title":"J. Neuroendocrinol."},{"key":"ref_117","first-page":"91","article-title":"Causes of death in patients with Huntington\u2019s disease and in unaffected first degree relatives","volume":"29","author":"Asger","year":"1992","journal-title":"J. Med. Genet."},{"key":"ref_118","first-page":"5845","article-title":"Neurocardiac dysregulation and neurogenic arrhythmias in a transgenic mouse model of Huntington\u2019s disease","volume":"590","author":"Kiriazis","year":"2012","journal-title":"J. Physiol. C"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Schroeder, A.M., Wang, H.B., Park, S., Jordan, M.C., Gao, F., Coppola, G., Fishbein, M.C., Roos, K.P., Ghiani, C.A., and Colwell, C.S. (2016). Cardiac Dysfunction in the BACHD Mouse Model of Huntington\u2019s Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147269"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Melkani, G.C., Trujillo, A.S., Ramos, R., Bodmer, R., Bernstein, S.I., Ocorr, K., and Lu, B. (2013). Huntington\u2019s Disease Induced Cardiac Amyloidosis Is Reversed by Modulating Protein Folding and Oxidative Stress Pathways in the Drosophila Heart. PLoS ONE, 9.","DOI":"10.1371\/journal.pgen.1004024"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Mielcarek, M., Inuabasi, L., Bondulich, M.K., Muller, T., Osborne, G.F., Franklin, S.A., Smith, D.L., Neueder, A., Rosinski, J., and Rattray, I. (2014). Dysfunction of the CNS-Heart Axis in Mouse Models of Huntington\u2019s Disease. PloS ONE, 10.","DOI":"10.1371\/journal.pgen.1004550"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1161\/HYPERTENSIONAHA.109.148635","article-title":"Heart Interleukin 6 Mediates Myocardial Fibrosis, Concentric Hypertrophy, and Diastolic Dysfunction in Rats","volume":"56","author":"Mclarty","year":"2010","journal-title":"Hypertension"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/ana.24406","article-title":"Cerebrovascular and blood-brain barrier impairments in Huntington\u2019s disease: Potential implications for its pathophysiology","volume":"78","author":"Sawiak","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"41316","DOI":"10.1038\/srep41316","article-title":"Impairment of blood-brain barrier is an early event in R6\/2 mouse model of Huntington Disease","volume":"7","author":"Amico","year":"2017","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6089\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:20:54Z","timestamp":1760138454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,29]]},"references-count":124,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23116089"],"URL":"https:\/\/doi.org\/10.3390\/ijms23116089","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,29]]}}}