Department of Physiology and McKusick-Nathans, Institute for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dis Model Mech. 2011 Sep;4(5):596-606. doi: 10.1242/dmm.007716. Epub 2011 Aug 4.
Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development.
近年来,利用小鼠模型,唐氏综合征(DS)患者认知障碍的治疗方法取得了显著进展。在这篇综述中,我们简要描述了代表药物测试结果目标的小鼠模型的表型、用于评估认知障碍的行为测试以及几种正在进行临床前研究或可能进行临床试验的药物的已知作用机制。在三体型大脑中,这些不同药物作用的靶点分布和受影响的途径存在重叠,这为 DS 研究和药物开发提供了新的途径。