LAUSR

For people with epilepsy, frontline treatment remains with antimice increase levels of Nwd1 and that Nwd1 levels are also higher in seizure drugs (ASDs), a group of over 20 different medicines available for this common, disabling brain disease. ASDs are effective in controlling seizures in approximately two-thirds of patients, but this leaves a very large number of people for whom seizures continue. This has devastating effects on quality of life and increases the risk for serious adverse events, including sudden unexplained death in epilepsy (SUDEP). In fact, the treatment gap is greater still. Since most ASDs work by dampening brain excitability, either by boosting inhibition or reducing excitability, serious side effects such as sedation are common, further reducing the quality of life. Finally, ASDs are not diseasemodifying, producing no long-term improvements to the underlying pathophysiology. As a result, there continues to be a major unmet need for more effective, safer ways to control seizures and modify the underlying hyperexcitable brain networks [1,2]. In an article in EBioMedicine, Yang and colleagues identify a promising new target for the treatment of epilepsy [3]. NACHT andWD repeat domain-containing protein 1, Nwd1, is a large (~175 kDa) cytoplasmic protein whose unusual name derives from structural features which are shared by various other molecules, some involved in the control of apoptosis [4]. One of these, Apaf-1, has previously been linked to the signaling pathways which result in cell death after prolonged seizures [5]. Some NACHT-containing proteins also serve in innate and adaptive immunity, including activating inflammatory signals [6]. This combination makes Nwd1 a very interesting protein, given that both excitatory communication and neuroinflammation are integral to the pathogenesis and maintenance of the epileptic state [7]. On this basis, and having noted the distribution of Nwd1 in the rodent brain [8], the authors hypothesize that the proteinmight be a component of the post-synaptic machinery linking surface ligand-gated ion channels to downstream intracellular molecules necessary for signal transduction. In an impressive study that neatly combines in vitro and in vivo animal studies with human data from patients with drugresistant epilepsy, they uncover a role for Nwd1 in the control of brain excitability. They first show that seizures induced by kainic acid in