4-Phenylbutyric acid and metformin decrease sensitivity to pentylenetetrazol-induced seizures in a malin knockout model of Lafora disease.

ABSTRACT: Lafora disease (LD) is a rare adolescent-onset progressive myoclonic epilepsy caused by loss-of-function mutations either in the EPM2A gene encoding laforin or in the EPM2B gene encoding malin. Mouse models with deletion in the Epm2a or the Epm2b gene show intracellular aggregates of polyglucosans (Lafora bodies) and neurological complications that resemble those observed in patients with LD. In the absence of laforin or malin expression, mice also show different degrees of hyperexcitability, as reflected by an enhanced response to the convulsant drug pentylenetetrazol (PTZ). Malin knockout mice treated with 4-phenylbutyric acid (4-PBA) and metformin showed decreased amounts of Lafora bodies and polyubiquitin protein aggregates in the brain, diminished neurodegeneration, and amelioration o

SUBMITTER: Sanchez-Elexpuru G 

PROVIDER: S-EPMC5491969 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature