The biochemical dynamics of the glycogen phosphatase laforin directly impact brain metabolism.

ABSTRACT: Laforin is the only known glycogen phosphatase. Mutations in the laforin gene lead to the fatal childhood dementia and progressive myoclonic epilepsy known as Lafora disease (LD). A hallmark of LD is aberrant, cytoplasmic, glycogen-like aggregates known as Lafora bodies. Surprisingly, recent reports indicate that overexpression of a phosphatase-deficient laforin mutant, with the catalytic cysteine mutated to serine (LCS), prevented the formation of Lafora bodies in a laforin KO mouse model. This finding led to questions regarding the biological relevance of laforin phosphatase activity and its role in LD etiology. In this study, we defined the in vitro and in vivo effects of the LCS mutation. LCS protein lacks catalytic activity but exhibits significantly higher binding to phosphate and lo

SUBMITTER: Brewer MK 

PROVIDER: S-EPMC12834914 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature