Phosphorylation of myelin regulatory factor by PRKG2 mediates demyelination in Huntington's disease.

ABSTRACT: Demyelination is a common pathological feature of a large number of neurodegenerative diseases including multiple sclerosis and Huntington's disease (HD). Laquinimod (LAQ) has been found to have therapeutic effects on multiple sclerosis and HD. However, the mechanism underlying LAQ's therapeutic effects remains unknown. Using HD mice that selectively express mutant huntingtin in oligodendrocytes and show demyelination, we found that LAQ reduces the Ser259 phosphorylation on myelin regulatory factor (MYRF), an oligodendrocyte-specific transcription factor promoting the expression of myelin-associated genes. The reduced MYRF phosphorylation inhibits MYRF's binding to mutant huntingtin and increases the expression of myelin-associated genes. We also found that PRKG2, a cGMP-activated protein

SUBMITTER: Yin P 

PROVIDER: S-EPMC9336218 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature