REST, a master transcriptional regulator in neurodegenerative disease

Curr Opin Neurobiol. 2018 Feb:48:193-200. doi: 10.1016/j.conb.2017.12.008. Epub 2018 Jan 30.


The restrictive element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor (NRSF) is a transcriptional repressor which acts via epigenetic remodeling to silence target genes. Emerging evidence indicates that REST is a master transcriptional regulator of neuron-specific genes not only in neurogenesis and neuronal differentiation, but also in differentiated neurons during the critical period in postnatal brain development, where it plays a role in fine-tuning of genes involved in synaptic plasticity, and in normal aging, where it promotes neuroprotection by repressing genes involved in oxidative stress and β-amyloid toxicity. This review focuses on recent findings that dysregulation of REST and REST-dependent epigenetic remodeling provide a central mechanism critical to the progressive neurodegeneration associated with neurologic disorders and diseases including global ischemia, stroke, epilepsy, Alzheimer's and Huntington's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Epigenomics
  • Gene Expression Regulation / physiology
  • Humans
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Repressor Proteins / physiology


  • RE1-silencing transcription factor
  • Repressor Proteins