Work

From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis

Year: 2009

Type: review

Abstract: 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.

Source: Journal of Intellectual Disability Research

DOI: 10.1111/j.1365-2788.2009.01208.x

Authors: D. Ehninger, P. J. De Vries, A. J. Silva

Institutions: University of California, Los Angeles, University of Cambridge, Cambridgeshire and Peterborough NHS Foundation Trust

Language: English

Topic: Tuberous Sclerosis Complex Research

Subfield: Genetics (clinical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Neurological Disorders and Stroke