Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1
Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1
复制标题
DOI：
10.1177/088307380201700813
复制
发表时间：
2002-08-01
影响因子：
1.9
通讯作者：
Silva, AJ
中科院分区：
文献类型：
--
作者：
Costa, RM;Silva, AJ
神经纤维瘤病1是影响人类神经功能的最常见的单基因疾病之一。NF1基因突变会导致细胞生长和分化异常，并导致各种学习障碍。神经纤维蛋白具有多种生化功能，如RAS-鸟苷三磷酸酶活性、腺苷环化酶调节和微管结合，所有这些对大脑功能都是至关重要的。我们回顾了在小鼠模型中的研究如何帮助揭开神经纤维瘤病1认知缺陷的分子和细胞机制。这些研究表明，与神经纤维瘤病I相关的学习障碍是由过度的RAS活性引起的，这导致伽马氨基丁酸(GABA(A))抑制增加和长期增强减少。这些发现使我们比以往任何时候都更接近于开发可能的治疗方法来治疗与神经纤维瘤病1相关的学习障碍。
Neurofibromatosis 1 is one of the most common single-gene disorders affecting neurologic function in humans. Mutations in the NF1 gene cause abnormalities in cell growth and differentiation and lead to a variety of learning disabilities. Neurofibromin has several biochemical functions, such as Ras-guanosine triphosphatase activity, adenylate cyclase modulation, and microtubule binding, all of which could be critical for brain function. We review how studies in mouse models are helping to unravel the molecular and cellular mechanisms underlying cognitive deficits in neurofibromatosis 1. These studies suggest that the learning disabilities associated with neurofibromatosis I are caused by excessive Ras activity that leads to increased gamma-aminobutyric acid (GABA(A)) inhibition and to decreased long-term potentiation. These findings have brought us closer than ever to the development of possible treatments for the learning disabilities associated with neurofibromatosis 1.