Neuroimmunology & Neurotherapeutics Laboratory, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.
Neuroimmunology & Neurotherapeutics Laboratory, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.
Front Neuroendocrinol. 2019 Apr;53:100744. doi: 10.1016/j.yfrne.2019.04.001. Epub 2019 Apr 17.
The transcriptional repressor REST (Repressor Element-1 Silencing Transcription factor) is a key modulator of the neuronal epigenome and targets genes involved in neuronal differentiation, axonal growth, vesicular transport, ion channel conductance and synaptic plasticity. Whilst its gene expression-modifying properties have been examined extensively in neuronal development, REST's response towards stress-induced neuronal insults has only recently been explored. Overall, REST appears to be an ideal candidate to fine-tune neuronal gene expression following different forms of cellular, neuropathological, psychological and physical stressors. Upregulation of REST is reportedly protective against premature neural stem cell depletion, neuronal hyperexcitability, oxidative stress, neuroendocrine system dysfunction and neuropathology. In contrast, neuronal REST activation has also been linked to neuronal dysfunction and neurodegeneration. Here, we highlight key findings and discrepancies surrounding our current understanding of REST's function in neuronal adaptation to stress and explore its potential role in neuronal stress resilience in the young and ageing brain.
转录抑制剂 REST（Repressor Element-1 Silencing Transcription factor）是神经元表观基因组的关键调节剂，它靶向参与神经元分化、轴突生长、囊泡运输、离子通道传导和突触可塑性的基因。虽然其基因表达修饰特性在神经元发育中已经得到了广泛研究，但 REST 对应激诱导的神经元损伤的反应最近才被探索。总的来说，REST 似乎是一个理想的候选者，可以在不同形式的细胞、神经病理学、心理和物理应激源后精细调节神经元的基因表达。据报道，REST 的上调可防止神经干细胞过早耗竭、神经元过度兴奋、氧化应激、神经内分泌系统功能障碍和神经病理学。相比之下，神经元 REST 的激活也与神经元功能障碍和神经退行性变有关。在这里，我们强调了当前对 REST 在神经元对应激的适应中的功能的关键发现和差异，并探讨了它在年轻和衰老大脑中神经元应激耐受力中的潜在作用。
