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REST: An epigenetic regulator of neuronal stress responses in the young and ageing brain

Mampay, Myrthe; Sheridan, Graham K.


Myrthe Mampay



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.


Mampay, M., & Sheridan, G. K. (2019). REST: An epigenetic regulator of neuronal stress responses in the young and ageing brain. Frontiers in Neuroendocrinology, 53, Article 100744.

Journal Article Type Review
Acceptance Date Apr 11, 2019
Online Publication Date Apr 17, 2019
Publication Date Apr 1, 2019
Deposit Date Aug 16, 2022
Journal Frontiers in Neuroendocrinology
Print ISSN 0091-3022
Electronic ISSN 1095-6808
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 53
Article Number 100744
Public URL
Publisher URL