Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease.

ABSTRACT: The CAG expansion of huntingtin (mHTT) associated with Huntington disease (HD) is a ubiquitously expressed gene, yet it prominently damages the striatum and cortex, followed by widespread peripheral defects as the disease progresses. However, the underlying mechanisms of neuronal vulnerability are unclear. Previous studies have shown that SUMO1 (small ubiquitin-like modifier-1) modification of mHtt promotes cellular toxicity, but the in vivo role and functions of SUMO1 in HD pathogenesis are unclear. Here, we report that SUMO1 deletion in Q175DN HD-het knockin mice (HD mice) prevented age-dependent HD-like motor and neurological impairments and suppressed the striatal atrophy and inflammatory response. SUMO1 deletion caused a drastic reduction in soluble mHtt levels and nuclear and extrace

SUBMITTER: Ramirez-Jarquin UN 

PROVIDER: S-EPMC8812691 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature