唐氏综合征认知障碍药物治疗的分子基础。
Molecular basis of pharmacotherapies for cognition in Down syndrome.
机构信息
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.
出版信息
Trends Pharmacol Sci. 2010 Feb;31(2):66-73. doi: 10.1016/j.tips.2009.10.010. Epub 2009 Dec 4.
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.
摘要
唐氏综合征（DS）患者的智力障碍范围从轻度正常到严重受损，对受影响个体及其家庭的生活质量有重大影响。由于 DS 的发病率仍约为每 700 例活产儿中有 1 例，且现在的预期寿命>50 年，因此开发针对认知缺陷的药物疗法是一个重要目标。DS 是由于人类 21 号染色体的额外拷贝引起的，并且由于其遗传异常通常被认为过于复杂而难以干预。然而，最近在一种 DS 小鼠模型中成功挽救学习/记忆障碍的研究结果表明，这种消极的观点可能没有根据。在这篇文章中，我们首先回顾了 DS 的表型、21 号染色体的基因内容和小鼠模型。然后我们讨论了在确定潜在治疗药物的靶点和临床前评估方面的最新进展和仍然存在的挑战。
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