title: Brain REST/NRSF Is Not Only a Silent Repressor but Also an Active Protector.
abstract: During neurogenesis, specific transcription factors are needed to repress neuronal genes in nonneuronal cells to ensure precise development. Repressor element-1 binding transcription factor (REST), or neuron-restrictive silencer factor (NRSF), has been shown to be an important regulator for the establishment of neuronal specificity. It restricts the expression of neuronal genes by binding to the neuron-restrictive silencer element (NRSE/RE1) domain in neuron-specific genes. REST/NRSF regulates many target genes in stem cells, nonneural cells, and neurons, which are involved in neuronal differentiation, axonal growth, vesicular transport, and release as well as ionic conductance. However, it is also regulated by some cytokines/regulators such as epigenetic factors (microRNAs) and even its truncated isoform. REST/NRSF is widely detected in brain regions and has been shown to be highly expressed in nonneuronal cells, but current findings also reveal that, at least in the human brain, it is also highly expressed in neurons and increases with ageing. However, its loss in expression and cytoplasmic translocation seems to play a pivotal role in several human dementias. Additionally, REST/NRSF knockdown leads to malformations in nerve and nonneural tissues and embryonic lethality. Altered REST/NRSF expression has been not only related to deficient brain functions such as neurodegenerative diseases, mental disorders, brain tumors, and neurobehavioral disorders but also highly correlated to brain injuries such as alcoholism and stroke. Encouragingly, several compounds such as valproic acid and X5050 that target REST/NRSF have been shown to be clinically effective at rescuing seizures or Niemann-Pick type C disease. Surprisingly, studies have also shown that REST/NRSF can function as an activator to induce neuronal differentiation. These findings strongly indicate that REST/NRSF is not only a classical repressor to maintain normal neurogenesis, but it is also a fine fundamental protector against neurodegeneration and other disorders and may be a novel potent therapeutic target for neural disturbances.
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.|School of Nursing, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Student Brigade, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.|School of Nursing, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.|School of Nursing, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China. zhangjqtmmu@yahoo.com.
authors.forename: Jiqiang
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D018696:Neuroprotective Agents; D020033:Protein Isoforms; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor
keywords: Brain injury; Neurodegenerative disease; Neurogenesis; Neuron-restrictive silencer factor (NRSF); Repressor element-1 binding transcription factor (REST)