Repurposing dimethyl fumarate as an antiepileptogenic and disease-modifying treatment for drug-resistant epilepsy.

Background: Epilepsy affects over 65 million people worldwide and significantly burdens patients, caregivers, and society. Drug-resistant epilepsy occurs in approximately 30% of patients and growing evidence indicates that oxidative stress contributes to the development of such epilepsies. Activation of the Nrf2 pathway, which is involved in cellular defense, offers a potential strategy for reducing oxidative stress and epilepsy treatment.

N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice.

The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and has an important role in the neurobiological processes underlying drug addiction. We have previously shown that an elevated ECS response to psychostimulant (cocaine) is involved in regulating the development and expression of cocaine-conditioned reward and sensitization. We therefore hypothesized that drug-induced elevation in endocannabinoids (eCBs) and/or eCB-like molecules (eCB-Ls) may represent a protective mechanism against drug insult, and boosting their levels exogenously may strengthen their neuroprotective effects.

Sestrin 3 promotes oxidative stress primarily in neurons following epileptic seizures in rats.

Epilepsy affects approximately 1% of the global population, with 30% of patients experiencing uncontrolled seizures despite treatment. Reactive oxygen species (ROS) and oxidative stress have been implicated in the pathogenesis of epilepsy. Sestrins are stress-inducible proteins that regulate the ROS response.

Drugs acting at TRPM7 channels inhibit seizure-like activity.

Transient receptor potential cation subfamily M7 (TRPM7) channels are ion channels permeable to divalent cations. They are abundantly expressed with particularly high expression in the brain. Previous studies have highlighted the importance of TRPM7 channels in brain diseases such as stroke and traumatic brain injury, yet evidence for a role in seizures and epilepsy is lacking.