Epilepsy and the many faces of Homer 1

Epilepsy is a debilitating neurological disorder that affects 3 million Americans. While several medical interventions are available for the treatment of this disorder including surgery and deep brain stimulation, the most common treatment is drug administration. However, there is a subset of individuals inflicted with epilepsy that will not respond to pharmaceutical treatment. As such, investigators have turned to investigating the genetic component of epileptogenesis in order to improve or even cure this disorder. The Homer family of scaffold proteins represents an intriguing pharmacological target due to its diverse roles in epileptogenesis and synaptic plasticity. Due to its ability to function as both a scaffold protein and a signal transduction molecule, Homer 1 represents a promising drug target. This article will highlight the varied role of Homer 1 gene expression in epilepsy, specifically in relation to glutamatergic signaling in addition to synaptic plasticity and cognitive/memory dysfunction. Special attention will also go to the potential role of Homer 1 in calcium regulation and hyperexcitability, and Homer-mediated synaptic reorganization of dendritic spines.