Trends Pharmacol Sci. 2010 Feb;31(2):66-73. Epub 2009 Dec 4.

Molecular basis of pharmacotherapies for cognition in Down syndrome.

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Department of Pediatrics, Intellectual and Developmental Disability Research Center, Human Medical Genetics and Neuroscience Programs, University of Colorado Denver, 12800 E 19(th) Avenue, Aurora, Colorado 80045, USA. katheleen.gardiner@ucdenver.edu

Abstract

Intellectual disability in Down syndrome (DS) ranges from low normal to severely impaired and has a significant impact on the quality-of-life of the individuals affected and their families. Because the incidence of DS remains at approximately 1 in 700 live births and the lifespan is now >50 years, development of pharmacotherapies for cognitive deficits is an important goal. DS is due to an extra copy of human chromosome 21 and has often been considered too complex a genetic abnormality to be amenable to intervention. However, recent successes in rescuing learning/memory impairments in a mouse model of DS suggest that this negative outlook may not be justified. In this contribution, we first review the DS phenotype, chromosome 21 gene content and mouse models. We then discuss recent successes and the remaining challenges in the identification of targets for and preclinical evaluation of potential therapeutics.

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PMCID:: PMC2815198

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