title: mTOR: A pathogenic signaling pathway in developmental brain malformations.
abstract: The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortical malformations associated with epilepsy and neurobehavioral disabilities. Investigation of mTOR signaling in these disorders provides for the first time exciting future avenues for assessment of biomarkers, patient stratification and prognostic measures as well as the opportunity for targeted therapy to regulate mTOR activity across all age groups. As we learn more about mTOR and its activity in the developing brain, many challenges will arise that must be overcome before widespread clinical therapeutics can be implemented.
authors: Department of Neurology, PENN Epilepsy Center, University of Pennsylvania, 3 West Gates Bldg, 3400 Spruce St, Philadelphia, PA 19104, USA. peter.crino@uphs.upenn.edu
authors: Peter B
authors: PB
authors: Crino
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001321:Autistic Disorder / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D054220:Malformations of Cortical Development / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D046912:Multiprotein Complexes; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D020123:Sirolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015415:Biomarkers; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D011506:Proteins; C476400:STRADA protein, human; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; C000624651:Tsc1 protein, mouse; C000624654:Tsc2 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020123:Sirolimus