NRSF/REST neuronal deficient mice are more vulnerable to the neurotoxin MPTP

Yu, Mei; Suo, Haiyun; Ming, Lei; Cai, Lei; Liu, Jie; Huang, Yu-Fang; Xu, Jing; Wang, Yancong; Zhu, Changhong; Fei, Jian; Huang, Fang

doi:10.1016/j.neurobiolaging.2012.06.002

Cited by 47 publications

(38 citation statements)

References 39 publications

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“…Previous ChIP-SACO 23 and ChIP-chip 24 studies also identified REST target genes involved in cell death. In addition, a recent study suggests that REST protects against the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a model of Parkinson’s disease 25 . Thus, REST may coordinate a stress response that is broadly neuroprotective in the aging brain.…”

Section: Discussionmentioning

confidence: 99%

REST and stress resistance in ageing and Alzheimer’s disease

Aron

Zullo

et al. 2014

Nature

677

758

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SummaryHuman neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during aging are unknown. Here we show that induction of the repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) is a universal feature of normal aging in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Chromatin immunoprecipitation with deep sequencing (ChIP-seq) and expression analysis show that REST represses genes that promote cell death and AD pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein (Aβ) toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional ortholog of REST, C. elegans SPR-4, also protects against oxidative stress and Aβ toxicity. During normal aging, REST is induced in part by cell non-autonomous Wnt signaling. However, in AD, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathologic misfolded proteins. Finally, REST levels during aging are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the aging brain.

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Section: Discussionmentioning

confidence: 99%

REST and stress resistance in ageing and Alzheimer’s disease

Aron

Zullo

et al. 2014

Nature

677

758

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“…In previous studies, we found the master neuronal gene silencer NRSF is involved in the pathogenesis of Parkinson's disease both in in vitro and in vivo models , Yu et al, 2013. (Lauffer et al, 2013).…”

Section: Discussionmentioning

confidence: 98%

“…Furthermore NRSF neuronal deficient mice are more vulnerable to the neurotoxin MPTP (Yu et al, 2013). Ohnuki et al also reported that a considerable number of NRSF target genes, such as TH, BDNF, UCH-L1 and mGluR1, were downregulated in the nigrostriatal pathway of MPTP-treated macaques (Ohnuki et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, NRSF regulates the transcription of its target genes via chromatin modifications. Recently, a large body of work shows that the NRSF protein is also expressed in mature neurons and involved in various neurological disorders M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 (Zuccato et al, 2003, Gao et al, 2011, Noh et al, 2012, Yu et al, 2013.…”

Section: Introductionmentioning

confidence: 99%

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NRSF is an essential mediator for the neuroprotection of trichostatin A in the MPTP mouse model of Parkinson's disease

et al. 2015

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“…The neuroprotection afforded by REST in aging brain transcends AD in that REST is also depleted in tissue from subjects with frontotemporal dementia and dementia with Lewy bodies [49]. Moreover, elevated REST expression in neurons of the substantia nigra is protective in an animal model of Parkinson’s disease [73]. These findings demonstrate that REST expression in aging neurons confers neuroprotection and implicate REST as a potential therapeutic target in both mild and severe cognitive impairment AD.…”

Section: Rest and Alzheimer’s Diseasementioning

confidence: 99%

REST, a master transcriptional regulator in neurodegenerative disease

Hwang

Zukin

2018

Current Opinion in Neurobiology

201

157

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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.

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NRSF/REST neuronal deficient mice are more vulnerable to the neurotoxin MPTP

Cited by 47 publications

References 39 publications

REST and stress resistance in ageing and Alzheimer’s disease

REST and stress resistance in ageing and Alzheimer’s disease

NRSF is an essential mediator for the neuroprotection of trichostatin A in the MPTP mouse model of Parkinson's disease

REST, a master transcriptional regulator in neurodegenerative disease

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