REST in the Road Map of Brain Development

Cell Mol Neurobiol. 2023 Oct;43(7):3417-3433. doi: 10.1007/s10571-023-01394-w. Epub 2023 Jul 30.

Abstract

Repressor element-1 silencing transcription factor (REST) or also known as neuron-restrictive silencing factor (NRSF), is the key initiator of epigenetic neuronal gene-expression modification. Identification of a massive number of REST-targeted genes in the brain signifies its broad involvement in maintaining the functionality of the nervous system. Additionally, REST plays a crucial role in conferring neuroprotection to the neurons against various stressors or insults during injuries. At the cellular level, nuclear localisation of REST is a key determinant for the functional transcriptional regulation of REST towards its target genes. Emerging studies reveal the implication of REST nuclear mislocalisation or dysregulation in several neurological diseases. The expression of REST varies depending on different types of neurological disorders, which has created challenges in the discovery of REST-targeted interventions. Hence, this review presents a comprehensive summary on the physiological roles of REST throughout brain development and its implications in neurodegenerative and neurodevelopmental disorders, brain tumours and cerebrovascular diseases. This review offers valuable insights to the development of potential therapeutic approaches targeting REST to improve pathologies in the brain. The important roles of REST as a key player in the nervous system development, and its implications in several neurological diseases.

Keywords: Brain development; Neurodegeneration; Neurodevelopment; Nuclear localisation; REST.

Publication types

  • Review

MeSH terms

  • Brain / metabolism
  • Brain Neoplasms* / pathology
  • Gene Expression Regulation
  • Humans
  • Repressor Proteins / metabolism
  • Transcription Factors* / genetics

Substances

  • Transcription Factors
  • Repressor Proteins