title: Candidate drug targets for prevention or modification of epilepsy.
abstract: Epilepsy is a prevalent neurological disorder afflicting nearly 50 million people worldwide. The disorder is characterized clinically by recurrent spontaneous seizures attributed to abnormal synchrony of brain neurons. Despite advances in the treatment of epilepsy, nearly one-third of patients are resistant to current therapies, and the underlying mechanisms whereby a healthy brain becomes epileptic remain unresolved. Therefore, researchers have a major impetus to identify and exploit new drug targets. Here we distinguish between epileptic effectors, or proteins that set the seizure threshold, and epileptogenic mediators, which control the expression or functional state of the effector proteins. Under this framework, we then discuss attempts to regulate the mediators to control epilepsy. Further insights into the complex processes that render the brain susceptible to seizures and the identification of novel mediators of these processes will lead the way to the development of drugs to modify disease outcome and, potentially, to prevent epileptogenesis.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322; email: nvarvel@emory.edu
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Varvel
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Jiang
authors.forename: Raymond
authors.initials: R
authors.lastname: Dingledine
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D058256:Brain Waves / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000927:Anticonvulsants
keywords: anticonvulsant; cytokines; disease modification; epileptogenesis; neuroinflammation; neuroprotection