Fragile X Syndrome and Targeted Treatment Trials
Fragile X Syndrome and Targeted Treatment Trials
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DOI：
10.1007/978-3-642-21649-7_17
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Berry-Kravis, Elizabeth
中科院分区：
文献类型：
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作者：
Hagerman, Randi;Lauterborn, Julie;Berry-Kravis, Elizabeth
近年来的工作揭示了脆性 X 综合征 (FXS) 的大量可能的新治疗靶点。动物模型的使用，包括脆弱的 X 基因敲除小鼠，其表现出与人类 FXS 非常相似的表型，已经在这一研究方向上取得了巨大进步。 FXS 中缺乏脆性 X 智力迟钝蛋白 (FMRP)，会导致其许多靶基因失调并通常过度表达，从而导致神经传递失衡和突触可塑性缺陷。在小鼠和苍蝇模型中，使用代谢型谷氨酸受体 (mGluR) 阻滞剂和γ氨基丁酸 (GABA) 激动剂已被证明可以有效逆转细胞和行为表型，并恢复正常的大脑连接。本章讨论了拟议的新药物治疗和教育干预措施。综合起来，这些不同的靶向治疗在减轻甚至逆转 FMRP 缺失引起的神经生物学异常方面显示出有希望的初步结果，并可能应用于包括自闭症在内的其他神经发育障碍。
Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism.