From human tissue to animal models: Insights into the pathogenesis of cortical dysplasia.
Cortical dysplasia, a malformation of the cerebral cortex of developmental origin, accounts for most cases of drug-resistant childhood epilepsy. Despite its prevalence, the genetic and molecular bases for the disease are not known for most cases. With the exception of tuberous sclerosis complex, a type of cortical malformation with known genetic etiology, no mutated genes have been identified that can lead to the neuroanatomic abnormalities observed in the patients. Furthermore, there are currently no animal models that completely recapitulate the features of the disease, hindering progress in developing new treatments for this devastating condition. In this article, I review some of the approaches that researchers in the field are undertaking to utilize the biopsy tissue obtained from patients with cortical dysplasia who are undergoing epilepsy surgery. These multifaceted approaches are providing a plethora of new information that is then utilized to generate and evaluate animal models and to further our understanding of the disease. These studies will enable the development of novel antiepileptic treatments for patients with cortical dysplasia and similar disorders.
D'Arcangelo
Gabriella
G
Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. darcangelo@biology.rutgers.edu
D000818:Animals; D001706:Biopsy / Q000706:statistics & numerical data; D002540:Cerebral Cortex / Q000473:pathology* / Q000601:surgery; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D007223:Infant; D054220:Malformations of Cortical Development / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D011506:Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics; D014402:Tuberous Sclerosis / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases