Parenti Ilaria, Rabaneda Luis G, Schoen Hanna, Novarino Gaia
Institute of Science and Technology Austria, Klosterneuburg, Austria.
Institute of Science and Technology Austria, Klosterneuburg, Austria.
Trends Neurosci. 2020 Aug;43(8):608-621. doi: 10.1016/j.tins.2020.05.004. Epub 2020 Jun 5.
Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of mutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches.
神经发育障碍（NDDs）是一类影响大脑发育和功能的疾病，其特点是具有广泛的遗传和临床变异性。在本综述中，我们讨论了影响NDDs临床表现的多种因素，特别关注基因易感性、突变负荷和双打击模型。尽管与NDDs相关的突变事件结构复杂，但所涉及的各种蛋白质似乎都汇聚于共同的途径，如突触可塑性/功能、染色质重塑因子和雷帕霉素哺乳动物靶标（mTOR）途径。对这些途径背后机制的深入理解有望促成可作为治疗靶点的候选物的鉴定。
