{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:35:40Z","timestamp":1788305740890,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Spanish MINECO and FEDER funds from the EU","doi-asserted-by":"publisher","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Spanish MINECO and FEDER funds from the EU","doi-asserted-by":"publisher","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Spanish MINECO and FEDER funds from the EU","doi-asserted-by":"publisher","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Spanish MINECO and FEDER funds from the EU","doi-asserted-by":"publisher","award":["CIPROM\/2021\/030"],"award-info":[{"award-number":["CIPROM\/2021\/030"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Unidad de Excelencia Mar\u00eda de Maeztu","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}]},{"name":"Unidad de Excelencia Mar\u00eda de Maeztu","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}]},{"name":"Unidad de Excelencia Mar\u00eda de Maeztu","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}]},{"name":"Unidad de Excelencia Mar\u00eda de Maeztu","award":["CIPROM\/2021\/030"],"award-info":[{"award-number":["CIPROM\/2021\/030"]}]},{"name":"GVA","award":["PID2019-110751RB-I00"],"award-info":[{"award-number":["PID2019-110751RB-I00"]}]},{"name":"GVA","award":["RED2018-102331-T"],"award-info":[{"award-number":["RED2018-102331-T"]}]},{"name":"GVA","award":["CEX2019-000919-M"],"award-info":[{"award-number":["CEX2019-000919-M"]}]},{"name":"GVA","award":["CIPROM\/2021\/030"],"award-info":[{"award-number":["CIPROM\/2021\/030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is an inherited neurodegenerative disorder considered a rare disease with a prevalence of 5.7 per 100,000 people. It is caused by an autosomal dominant mutation consisting of expansions of trinucleotide repeats that translate into poly-glutamine enlarged mutant huntingtin proteins (mHTT), which are particularly deleterious in brain tissues. Since there is no cure for this progressive fatal disease, searches for new therapeutic approaches are much needed. The small molecule pytren-4QMn (4QMn), a highly water-soluble mimic of the enzyme superoxide dismutase, has shown in vivo beneficial anti-inflammatory activity in mice and was able to remove mHTT deposits in a C. elegans model of HD. In this study, we assessed 4QMn therapeutic potential in zQ175 neo-deleted knock-in mice, a model of HD that closely mimics the heterozygosity, genetic injury, and progressive nature of the human disease. We provide evidence that 4QMn has good acute and chronic tolerability, and can cross the blood\u2013brain barrier, and in male, but not female, zQ175 mice moderately ameliorate HD-altered gene expression, mHtt aggregation, and HD disease phenotype. Our data highlight the importance of considering sex-specific differences when testing new therapies using animal models and postulate 4QMn as a potential novel type of small water-soluble metal complex that could be worth further investigating for its therapeutic potential in HD, as well as in other polyglutamine diseases.<\/jats:p>","DOI":"10.3390\/ijms242015153","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T10:04:39Z","timestamp":1697191479000},"page":"15153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Small Molecule Pytren-4QMn Metal Complex Slows down Huntington\u2019s Disease Progression in Male zQ175 Transgenic Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Mari\u00e1n","family":"Merino","sequence":"first","affiliation":[{"name":"Bionos Biotech SL, Biopolo Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Bionos Biotech SL, Biopolo Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00aa Carmen","family":"Tronch","sequence":"additional","affiliation":[{"name":"Bionos Biotech SL, Biopolo Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Virginia","family":"S\u00e1nchez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Bionos Biotech SL, Biopolo Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00aa Paz","family":"Clares","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica e Inorg\u00e1nica, Instituto de Ciencia Molecular, Universidad de Valencia, 46980 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-3161","authenticated-orcid":false,"given":"Antonio","family":"Garc\u00eda-Espa\u00f1a","sequence":"additional","affiliation":[{"name":"Bionos Biotech SL, Biopolo Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4601-6505","authenticated-orcid":false,"given":"Enrique","family":"Garc\u00eda-Espa\u00f1a","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica e Inorg\u00e1nica, Instituto de Ciencia Molecular, Universidad de Valencia, 46980 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Mullor","sequence":"additional","affiliation":[{"name":"Bionos Biotech SL, Biopolo Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s Disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3233\/JHD-210515","article-title":"Temporal Phenotypic Changes in Huntington\u2019s Disease Models for Preclinical Studies","volume":"11","author":"Smith","year":"2022","journal-title":"J. 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