ArticleRare diseases (Austin, Tex.)2016
The calpain-suppressing effects of olesoxime in Huntington's disease.
Article in Rare diseases (Austin, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- A Novel Huntington's Disease Assessment Platform to Support Future Drug Discovery and Development.International journal of molecular sciences · 2022Article
- Calpains as novel players in the molecular pathogenesis of spinocerebellar ataxia type 17.Cellular and molecular life sciences : CMLS · 2022Article
- Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity.Frontiers in molecular neuroscience · 2022Review
- Calpain-1 ablation partially rescues disease-associated hallmarks in models of Machado-Joseph disease.Human molecular genetics · 2020Article
- Differential regulation of Kidins220 isoforms in Huntington's disease.Brain pathology (Zurich, Switzerland) · 2020Article
- Calpain proteolytic systems counteract endothelial cell adaptation to inflammatory environments.Inflammation and regeneration · 2020Review
- Cholesterol and the Safety Factor for Neuromuscular Transmission.International journal of molecular sciences · 2019Review
- Killing Two Angry Birds with One Stone: Autophagy Activation by Inhibiting Calpains in Neurodegenerative Diseases and Beyond.BioMed research international · 2019Review
- A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease.Scientific reports · 2018Article
- Calpain research for drug discovery: challenges and potential.Nature reviews. Drug discovery · 2016Review
Corrections and comments
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Authors and funding
5 authors.
Funding
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Abstract
Olesoxime, a small molecule drug candidate, has recently attracted attention due to its significant beneficial effects in models of several neurodegenerative disorders including Huntington's disease. Olesoxime's neuroprotective effects have been assumed to be conveyed through a direct, positive influence on mitochondrial function. In a long-term treatment study in BACHD rats, the latest rat model of Huntington's disease, olesoxime revealed a positive influence on mitochondrial function and improved specific behavioral and neuropathological phenotypes. Moreover, a novel target of the compound was discovered, as olesoxime was found to suppress the activation of the calpain proteolytic system, a major contributor to the cleavage of the disease-causing mutant huntingtin protein into toxic fragments, and key player in degenerative processes in general. Results from a second model of Huntington's disease, the Hdh (Q111) knock-in mouse, confirm olesoxime's calpain-suppressing effects and support the therapeutic value of olesoxime for Huntington's disease and other disorders involving calpain overactivation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.