Stabilizing dendritic structure as a novel therapeutic approach for epilepsy.
People with epilepsy often experience long-term cognitive dysfunction and other neurological deficits, including memory loss, learning disabilities and neurobehavioral disorders, which may exhibit a progressive course correlating with worsening seizure control. Furthermore, a third of epilepsy patients have seizures that are intractable to all available treatments. Thus, novel therapies for seizures and the neurological comorbidities of epilepsy are desperately needed. As most current treatments are merely symptomatic therapies that suppress seizures, epilepsy researchers have recently realized the critical need for novel therapeutic strategies targeting the underlying mechanisms of epileptogenesis and seizure-related brain injury. Yet, to date, few such antiepileptogenic therapies have emerged or are even in developmental stages. Although many seizure medications modulate the functional or physiological activity of neurons, the methods for stabilizing the structure of neurons are relatively unexplored therapeutic strategies for epilepsy. Human pathological studies and animal models of epilepsy demonstrate obvious structural abnormalities in dendrites of neurons, which could contribute to neuronal dysfunction, epileptogenesis and cognitive/neurological deficits in epilepsy patients. This dendritic injury may be caused by activity-dependent breakdown of cytoskeletal elements, such as actin. Mechanistically targeted approaches to limit seizure-related structural changes in dendrites may represent a novel therapeutic strategy for treating epilepsy and its complications.
Wong
Michael
M
Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. wong_m@wustl.edu.
D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D003712:Dendrites / Q000473:pathology* / Q000502:physiology*; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006801:Humans