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There is no currently available cure or rescue for dying brain cells. Viable therapeutics for any of these disorders would be a breakthrough and provide relief for the large number of affected patients and their families. Neurodegeneration is accompanied by elevated oxidative damage and inflammation. While natural antioxidants have largely failed in clinical trials, preclinical phenotyping of the unnatural, mitochondrial targeted nitroxide, XJB-5-131, bodes well for further translational development in advanced animal models or in humans. Here we consider the usefulness of synthetic antioxidants for the treatment of Huntington\u2019s disease. The mitochondrial targeting properties of XJB-5-131 have great promise. It is both an electron scavenger and an antioxidant, reducing both somatic expansion and toxicity simultaneously through the same redox mechanism. By quenching reactive oxygen species, XJB-5-131 breaks the cycle between the rise in oxidative damage during disease progression and the somatic growth of the CAG repeat which depends on oxidation.<\/jats:p>","DOI":"10.3233\/jhd-210510","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T12:14:59Z","timestamp":1639484099000},"page":"3-15","source":"Crossref","is-referenced-by-count":14,"title":["A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington\u2019s Disease"],"prefix":"10.1177","volume":"11","author":[{"given":"Pater","family":"Wipf","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aris A.","family":"Polyzos","sequence":"additional","affiliation":[{"name":"Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia T.","family":"McMurray","sequence":"additional","affiliation":[{"name":"Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JHD-210510_ref1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s disease facts and figures. 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