Linking brain tumors and epileptic seizures

Abstract

Mutationally activated BRAF^V600E influences the behavior of different types of cells in the brain and leads to promotion of seizures as well as brain tumors, indicating how both can be pharmacologically targeted in the clinic.

Fig. 1 |. The role of BRAF^V600E signaling and REST in GG-associated intractable epilepsy.

Koh et al. find that expression of mutationally activated BRAF^V600E in neural stem cells during early brain development results in dysplastic, non-neoplastic, epileptogenic neurons. By contrast, BRAF^V600E expression in cells that develop along the glial differentiation pathway results in neoplastic but nonepileptogenic cells. BRAF^V600E-driven GG-associated LEAT seizures are driven by constitutive BRAF^V600E→ MEK→ ERK signaling that drives expression of c-MYC that in turn promotes elevated expression of REST. Elevated REST expression leads to transcriptional repression of mRNAs associated with neuronal function resulting in the development of intractable epileptic seizures.