ERIC Number: EJ856488
Record Type: Journal
Publication Date: 2009-Oct
Abstractor: As Provided
Reference Count: 105
From mTOR to Cognition: Molecular and Cellular Mechanisms of Cognitive Impairments in Tuberous Sclerosis
Ehninger, D.; de Vries, P. J.; Silva, A. J.
Journal of Intellectual Disability Research, v53 n10 p838-851 Oct 2009
Background: Tuberous sclerosis (TSC) is a multi-system disorder caused by heterozygous mutations in the "TSC1" or "TSC2" gene and is often associated with neuropsychiatric symptoms, including intellectual disability, specific neuropsychological deficits, autism, other behavioural disorders and epilepsy. Method: Here, we review evidence from animal models of TSC for the role of specific molecular and cellular processes in the pathogenesis of cognitive, developmental and epilepsy-related manifestations seen in the disorder. Results: Recent evidence shows that, in animal models, disinhibited mTOR (mammalian target of rapamycin) signalling substantially contributes to neuropsychiatric phenotypes, including cognitive deficits and seizures. We discuss potential pathogenetic mechanisms involved in the cognitive phenotypes of TSC and present implications regarding mTOR inhibitor-based treatments for TSC-related neuropsychiatric features. Conclusions: Results suggest that reversing the underlying molecular deficits of TSC with rapamycin or other mTOR inhibitors could result in clinically significant improvements of cognitive function and neurological symptoms, even if treatments are started in adulthood.
Descriptors: Epilepsy, Mental Retardation, Seizures, Pathology, Etiology, Diseases, Molecular Structure, Neurological Impairments, Genetic Disorders, Animals, Cognitive Ability, Developmental Delays, Symptoms (Individual Disorders), Psychiatry
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Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Authoring Institution: N/A