The tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems. The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities, and autism. Progress over the past 15 years has demonstrated that the TSC1 or TSC2 encoded proteins modulate cell function via the mTOR signaling cascade and serve as keystones in regulating cell growth and proliferation. The mTOR pathway provides an intersection for an intricate network of protein cascades that respond to cellular nutrition, energy levels, and growth-factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body size, dendritic arborization, axonal outgrowth and targeting, neuronal migration, cortical lamination, and spine formation. Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients.
Departments of Neurology and Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Ksenia A
KA
Orlova
Peter B
PB
Crino
D000818:Animals; D001369:Axons / Q000502:physiology; D002455:Cell Division; D002540:Cerebral Cortex / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D006222:Hamartoma / Q000209:etiology; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009422:Nervous System Diseases / Q000453:epidemiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D013131:Spine / Q000254:growth & development; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C515347:TSC1 protein, Drosophila; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases