Suppressor of cytokine signaling 2 is induced in Huntington's Disease and involved in autophagy

Suppressor of cytokine signaling (SOCS) proteins are primarily feedback inhibitors of cytokine signaling. The two conserved domains of SOCS proteins have distinct functions. Src homology 2 (SH2) domain inhibits cytokine receptor, while SOCS box acts as an E3 ubiquitin ligase. SOCS2, a cytokine signaling suppressor, has been primarily implicated in regulating inflammatory conditions in neuronal diseases. However, SOCS proteins have been suggested to play diverse roles in healthy and diseased nervous system including neurodegenerative disorders. In this study, SOCS2 was found to be upregulated in Huntington's disease and was substantially induced in extended polyglutamine (polyQ)-expressing striatal cells. The induced level was augmented under aging conditions. In extended polyQ-expressing cells, downregulated SOCS2 improved autophagic dysfunction rather than altered inflammatory conditions. Overall, we suggest that SOCS2 involves in regulating autophagy by functioning as an E3 ligase in extended polyQ conditions, and consequently regulates cell damage and cell death type. Overall design: To examine gene expression changes in subregions of the brain (striatum and cortex) according to age (before and after the onset of disease symptoms) in Huntington's disease mice, total mRNA was isolated from tissues of striatal and cortical subregions of the brain of HD mice (R6/2) and WT mice (normal R6/2 littermate) of the same age, and RNA-seq was performed. Gene expression profiling analysis of RAN-seq data from each mouse brain tissue.