The R6 lines of transgenic mice: a model for screening new therapies for Huntington's disease.
Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene that results in cortical and striatal degeneration, and mutant huntingtin aggregation. Current treatments are unsatisfactory. R6 transgenic mice replicate many features of the human condition, show early onset of symptoms and fast disease progression, being one of the most used models for therapy screening. Here we review the therapies that have been tested in these mice: environmental enrichment, inhibition of histone deacetylation and methylation, inhibition of misfolding and oligomerization, transglutaminase inhibition, rescue of metabolic impairment, amelioration of the diabetic phenotype, use of antioxidants, inhibition of excitotoxicity, caspase inhibition, transplantation, genetic manipulations, and restoration of neurogenesis. Although many of these treatments were beneficial in R6 mice, they may not be as effective in HD patients, and thus the search for a combination of therapies that will rescue the human condition continues.
Gil
Joana M
JM
Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, V8W 2Y2, Canada. jgil@uvic.ca
Rego
A Cristina
AC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D016380:Brain Tissue Transplantation / Q000379:methods / Q000639:trends; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology
D018696:Neuroprotective Agents