| Title: | The Urine Metabolome of R6/2 and zQ175DN Huntington's Disease Mouse Models |
| Author(s): | Speziale R; Montesano C; Di Pietro G; Cicero DO; Summa V; Monteagudo E; Orsatti L; |
| Address: | "Experimental Pharmacology Department, IRBM SpA, Via Pontina km 30.600, 00071 Pomezia, Italy. Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy. Department of Chemical Sciences and Technology, University of Rome 'Tor Vergata', Via Cracovia 50, 00133 Roma, Italy. Department of Pharmacy, University of Napoli 'Federico II', Corso Umberto I 40, 80138 Napoli, Italy. CHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USA" |
| ISSN/ISBN: | 2218-1989 (Print) 2218-1989 (Electronic) 2218-1989 (Linking) |
| Abstract: | "Huntington's disease (HD) is caused by the expansion of a polyglutamine (polyQ)-encoding tract in exon 1 of the huntingtin gene to greater than 35 CAG repeats. It typically has a disease course lasting 15-20 years, and there are currently no disease-modifying therapies available. Thus, there is a need for faithful mouse models of HD to use in preclinical studies of disease mechanisms, target validation, and therapeutic compound testing. A large variety of mouse models of HD were generated, none of which fully recapitulate human disease, complicating the selection of appropriate models for preclinical studies. Here, we present the urinary liquid chromatography-high-resolution mass spectrometry analysis employed to identify metabolic alterations in transgenic R6/2 and zQ175DN knock-in mice. In R6/2 mice, the perturbation of the corticosterone metabolism and the accumulation of pyrraline, indicative of the development of insulin resistance and the impairment of pheromone excretion, were observed. Differently from R6/2, zQ175DN mice showed the accumulation of oxidative stress metabolites. Both genotypes showed alterations in the tryptophan metabolism. This approach aims to improve our understanding of the molecular mechanisms involved in HD neuropathology, facilitating the selection of appropriate mouse models for preclinical studies. It also aims to identify potential biomarkers specific to HD" |
| Keywords: | Huntington's disease R6/2 mice mass spectrometry urine metabolome zQ175DN mice; |
| Notes: | "PubMed-not-MEDLINESpeziale, Roberto Montesano, Camilla Di Pietro, Giulia Cicero, Daniel Oscar Summa, Vincenzo Monteagudo, Edith Orsatti, Laura eng Switzerland 2023/08/25 Metabolites. 2023 Aug 18; 13(8):961. doi: 10.3390/metabo13080961" |
