Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Trends Neurosci. 2013 Apr;36(4):237-47. doi: 10.1016/j.tins.2012.12.002. Epub 2013 Jan 8.
Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and dissect mechanistically the molecular and cellular bases underlying cognitive dysfunction. In this review, we discuss Nf1 fly and mouse systems that mimic many of the cognitive abnormalities seen in children with NF1. Further, we describe discoveries from these models that have uncovered defects in the regulation of Ras activity, cAMP generation, and dopamine homeostasis as key mechanisms important for cognitive dysfunction in children with NF1.
认知功能障碍，包括学习、行为和注意力方面的显著损伤，在普通人群中超过 10%的儿童中被发现。然而，在常见的遗传性癌症易感性综合征，神经纤维瘤病 1 型（NF1）中，这些认知缺陷的患病率接近 70%。作为一种单基因疾病，NF1 提供了一个独特的遗传工具，可以识别和从机制上剖析导致认知功能障碍的分子和细胞基础。在这篇综述中，我们讨论了模拟 NF1 患儿许多认知异常的 Nf1 蝇和鼠系统。此外，我们描述了这些模型中的发现，这些发现揭示了 Ras 活性、cAMP 生成和多巴胺动态平衡调节的缺陷是 NF1 患儿认知功能障碍的关键机制。
