Chronic 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Treatment Induces Phenotypic Changes in Skeletal Muscle, but Does Not Improve Disease Outcomes in the R6/2 Mouse Model of Huntington's Disease.

摘要: Huntington’s disease (HD) is an autosomal dominant neurodegenerative genetic disorder characterized by motor, cognitive and psychiatric symptoms. It well established that regular physical activity supports brain health, benefiting function, mental health as structure plasticity. Exercise mimetics (EMs) are a group of drugs small molecules target signaling pathways in skeletal muscle known to be activated endurance exercise. The EM 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) has been shown induce benefits healthy mice. Since AICAR does not readily cross the blood-brain barrier, its beneficial effect on ascribed impact muscle. Our objective, therefore, was examine chronic treatment muscular neurological pathology mouse model HD. To this end, R6/2 mice were treated with for 8 weeks underwent neurobehavioral testing. Under our conditions, increased expression PGC-1α, powerful phenotypic modifier muscle, induced expected shift towards more oxidative phenotype However, failed HD progression. Indeed, deficits, striatal mHTT aggregate density, atrophy mitigated administration AICAR. Although adaptations seen following may still provide therapeutically relevant patients limited mobility, findings indicate under experimental had no several hallmarks