Proteasomal-Dependent Aggregate Reversal and Absence of Cell Death in a Conditional Mouse Model of Huntington's Disease

摘要: Neuronal intranuclear inclusions are a histopathological hallmark of Huntington's disease. Nevertheless, the precise mechanism by which they formed and their relevance to neuronal cell death and/or dysfunction remains unclear. We recently generated conditional mouse model disease (HD94) in silencing expression mutated huntingtin led disappearance aggregates amelioration behavioral phenotype. Here, we analyze primary striatal cultures from HD94 mice explore dynamics aggregate formation reversal, possible mechanisms involved, correlation between death. In parallel, examine symptomatic adult similar studies explored relationship clearance reversal. report that, culture, reversal were rapid processes, such that 2 d transgene formation, 5 suppression disappearance. mice, full mutant was more than reported previously preceded motor recovery several weeks. Furthermore, proteasome inhibitor lactacystin inhibited observed thus indicating is balance rate synthesis its degradation proteasome. Finally, neither nor compromised viability cultures. This correlated with lack demonstrating dysfunction, not loss, triggered underlies symptomatology.