Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
INSERM 1024, Ecole Normale Supérieure, Paris, France.
J Comp Physiol B. 2024 Jun;194(3):253-263. doi: 10.1007/s00360-023-01531-3. Epub 2024 Feb 24.
Individuals with neurodevelopmental disorders experience persistent sleep deficits, and there is increasing evidence that sleep dysregulation is an underlying cause, rather than merely an effect, of the synaptic and behavioral defects observed in these disorders. At the molecular level, dysregulation of the synaptic proteome is a common feature of neurodevelopmental disorders, though the mechanism connecting these molecular and behavioral phenotypes is an ongoing area of investigation. A role for eIF2α in shifting the local proteome in response to changes in the conditions at the synapse has emerged. Here, we discuss recent progress in characterizing the intersection of local synaptic translation and sleep and propose a reciprocal mechanism of dysregulation in the development of synaptic plasticity defects in neurodevelopmental disorders.
患有神经发育障碍的个体经历持续的睡眠不足,越来越多的证据表明,睡眠失调是突触和行为缺陷的根本原因,而不仅仅是这些障碍中观察到的结果。在分子水平上,突触蛋白组的失调是神经发育障碍的共同特征,尽管连接这些分子和行为表型的机制仍在研究中。eIF2α 在响应突触处条件变化而局部改变蛋白质组的作用已经显现。在这里,我们讨论了描述局部突触翻译与睡眠之间的交点的最新进展,并提出了神经发育障碍中突触可塑性缺陷发展的失调的一个相互作用机制。