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It occurs due to a mutation in the huntingtin (or IT19) gene with an abnormal CAG repeat, leading to a variable length N-terminal polyglutamine chain (poly-Q). Like most neurodegenerative diseases, HD is characterized by the abnormal deposition and aggregation of proteins in the cell, which impairs the proteostasis and disrupts cellular homeostasis. In this study, we used Caenorhabditis elegans as an animal model due to its easy genetic manipulation and high homology of genes and signaling pathways with mammals. Worms were exposed to diphenyl diselenide (PhSe)2 at 25, 50 and 100 \u03bcM, and then we analyzed the polyQ aggregation, neurodegeneration, touch response, reactive oxygen species (ROS) levels, lifespan and health span. In addition, we analyzed the involvement of the transcription factor DAF-16, a FOXO-ortholog, and the downstream heat-shock protein-16.2 (HSP-16.2) and superoxide dismutase-3 (SOD-3). Our data demonstrate that chronic treatment with (PhSe)2 reduced polyQ aggregation in muscle and polyQ mediated neuronal cell death of sensory neurons ASH, as well as maintaining the neuronal function. In addition, (PhSe)2 decreased ROS levels and extended the lifespan and health span of wild type and PolyQ mutant worms. The mechanism proposed is the activation of DAF-16, HSP-16.2 and SOD-3 in whole body tissues to increase the antioxidant capacity and regulation of proteostasis, decreasing PolyQ aggregation and toxicity and reducing ROS levels, leading to an increase in lifespan, and healthspan. Our findings provide new clues for treatment strategies for neurodegenerative diseases and other diseases caused by age-related protein aggregation.<\/jats:p>","DOI":"10.1039\/d0mt00074d","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T13:00:28Z","timestamp":1588683628000},"page":"1142-1158","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Diphenyl diselenide protects a <i>Caenorhabditis elegans<\/i> model for Huntington\u2019s disease by activation of the antioxidant pathway and a decrease in protein aggregation"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-3793","authenticated-orcid":false,"given":"Fabiane","family":"Bicca Obetine Baptista","sequence":"first","affiliation":[{"name":"Universidade Federal de Santa Maria, Centro de Ci\u00eancias Naturais e Exatas, Departamento de Bioqu\u00edmica e Biologia Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Camobi, 97105-900, Santa Maria, RS, Brazil. Tel: +55-55-3220-9522"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Priscilla","family":"Arantes","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Maria, Centro de Ci\u00eancias Naturais e Exatas, Departamento de Bioqu\u00edmica e Biologia Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Camobi, 97105-900, Santa Maria, RS, Brazil. Tel: +55-55-3220-9522"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-3316","authenticated-orcid":false,"given":"Marina Lopes","family":"Machado","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Maria, Centro de Ci\u00eancias Naturais e Exatas, Departamento de Bioqu\u00edmica e Biologia Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Camobi, 97105-900, Santa Maria, RS, Brazil. Tel: +55-55-3220-9522"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Franzen","family":"da Silva","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Maria, Centro de Ci\u00eancias Naturais e Exatas, Departamento de Bioqu\u00edmica e Biologia Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Camobi, 97105-900, Santa Maria, RS, Brazil. Tel: +55-55-3220-9522"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Marafiga Cordeiro","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Maria, Centro de Ci\u00eancias Naturais e Exatas, Departamento de Bioqu\u00edmica e Biologia Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Camobi, 97105-900, Santa Maria, RS, Brazil. Tel: +55-55-3220-9522"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00e1ssia Limana","family":"da Silveira","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Maria, Centro de Ci\u00eancias Naturais e Exatas, Departamento de Bioqu\u00edmica e Biologia Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Camobi, 97105-900, Santa Maria, RS, Brazil. Tel: +55-55-3220-9522"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6453-7902","authenticated-orcid":false,"given":"Felix Alexandre Antunes","family":"Soares","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Maria, Centro de Ci\u00eancias Naturais e Exatas, Departamento de Bioqu\u00edmica e Biologia Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Camobi, 97105-900, Santa Maria, RS, Brazil. Tel: +55-55-3220-9522"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"issue":"10","key":"2021121004470258600_cit1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nrg1686","article-title":"History of genetic disease: the molecular genetics of Huntington disease\u2014a history","volume":"6","author":"Bates","year":"2005","journal-title":"Nat. Rev. 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