Wnt/β-catenin signaling as a potential target for novel epilepsy therapies

Epilepsy is one of the most common neurological disorders, and yet many afflicted individuals are resistant to all available therapeutic treatments. Existing pharmaceutical treatments function primarily to reduce hyperexcitability and prevent seizures, but fail to influence the underlying pathophysiology of the disorder. Recently, research efforts have focused on identifying alternative mechanistic targets for anti-epileptogenic therapies that can prevent the development of chronic epilepsy. The Wnt/β-catenin pathway, one possible target, has been demonstrated to be disrupted in both acute and chronic phases of epilepsy. Wnt/β-catenin signaling can regulate many seizure-induced changes in the brain, including neurogenesis and neuronal death, as well as can influence seizure susceptibility and potentially the development of chronic epilepsy. Several genome-wide studies and in vivo knockout animal models have provided evidence for an association between disrupted Wnt/β-catenin signaling and epilepsy. Furthermore, approved pharmaceutical drugs and other small molecule compounds that target components of the β-catenin destruction complex or antagonize endogenous inhibitors of the pathway have shown to be protective following seizures. However, additional studies are needed to determine the optimal time period in which modulation of the pathway may be most beneficial. Overall, disrupted molecular networks such as Wnt/β-catenin signaling, could be a promising anti-epileptogenic target for future epilepsy therapies.