Neurobiol Dis 2021 Jun 18:105427. Epub 2021 Jun 18.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, United States of America; Medical Investigations of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis, CA 95817, USA. Electronic address:
CGG expansions between 55 and 200 in the 5'-untranslated region of the fragile-X mental retardation gene (FMR1) increase the risk of developing the late-onset debilitating neuromuscular disease Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). While the science behind this mutation, as a paradigm for RNA-mediated nucleotide triplet repeat expansion diseases, has progressed rapidly, no treatment has proven effective at delaying the onset or decreasing morbidity, especially at later stages of the disease. Here, we demonstrated the beneficial effect of the phytochemical sulforaphane (SFN), exerted through NRF2-dependent and independent manner, on pathways relevant to brain function, bioenergetics, unfolded protein response, proteosome, antioxidant defenses, and iron metabolism in fibroblasts from FXTAS-affected subjects at all disease stages. Read More