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通过RAS病理解智力残疾

Understanding intellectual disability through RASopathies.

作者信息

San Martín Alvaro, Pagani Mario Rafael

机构信息

Genetics of Learning Laboratory, Systems Neuroscience Section, Department of Physiology and Biophysics, School of Medicine, University of Buenos Aires, IFIBIO-Houssay-CONICET, C1121ABG Buenos Aires, Argentina.

Genetics of Learning Laboratory, Systems Neuroscience Section, Department of Physiology and Biophysics, School of Medicine, University of Buenos Aires, IFIBIO-Houssay-CONICET, C1121ABG Buenos Aires, Argentina.

出版信息

J Physiol Paris. 2014 Sep-Dec;108(4-6):232-9. doi: 10.1016/j.jphysparis.2014.05.003. Epub 2014 May 21.

Abstract

Intellectual disability, commonly known as mental retardation in the International Classification of Disease from World Health Organization, is the term that describes an intellectual and adaptive cognitive disability that begins in early life during the developmental period. Currently the term intellectual disability is the preferred one. Although our understanding of the physiological basis of learning and learning disability is poor, a general idea is that such condition is quite permanent. However, investigations in animal models suggest that learning disability can be functional in nature and as such reversible through pharmacology or appropriate learning paradigms. A fraction of the cases of intellectual disability is caused by point mutations or deletions in genes that encode for proteins of the RAS/MAP kinase signaling pathway known as RASopathies. Here we examined the current understanding of the molecular mechanisms involved in this group of genetic disorders focusing in studies which provide evidence that intellectual disability is potentially treatable and curable. The evidence presented supports the idea that with the appropriate understanding of the molecular mechanisms involved, intellectual disability could be treated pharmacologically and perhaps through specific mechanistic-based teaching strategies.

摘要

智力障碍,在世界卫生组织的《国际疾病分类》中通常被称为精神发育迟缓,是一个描述始于发育早期的智力和适应性认知障碍的术语。目前,“智力障碍”一词是更常用的术语。尽管我们对学习和学习障碍的生理基础了解甚少,但总体上认为这种情况相当持久。然而,对动物模型的研究表明,学习障碍本质上可能是功能性的,因此可以通过药理学或适当的学习范式逆转。一部分智力障碍病例是由编码RAS/MAP激酶信号通路蛋白质的基因突变或缺失引起 的,这些疾病被称为RAS病。在这里,我们研究了目前对这组遗传疾病所涉及分子机制的理解,重点关注那些提供证据表明智力障碍具有潜在可治疗性和可治愈性的研究。所呈现的证据支持这样一种观点,即通过对所涉及分子机制的适当理解,智力障碍可以通过药理学治疗,也许还可以通过基于特定机制的教学策略来治疗。

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