REST and Stress Resistance in Ageing and Alzheimer’s Disease

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REST and Stress Resistance in Ageing and Alzheimer’s Disease

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Title: REST and Stress Resistance in Ageing and Alzheimer’s Disease
Author: Lu, Tao; Aron, Liviu; Zullo, Joseph M.; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek Mark; Liu, Xiaole (Shirley) Shirley; Bennett, David A.; Colaiacovo, Monica P.; Yankner, Bruce Albert

Note: Order does not necessarily reflect citation order of authors.

Citation: Lu, Tao, Liviu Aron, Joseph Zullo, Ying Pan, Haeyoung Kim, Yiwen Chen, Tun-Hsiang Yang, et al. 2014. REST and Stress Resistance in Ageing and Alzheimer’s Disease. Nature 507, no. 7493: 448–454. doi:10.1038/nature13163
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Abstract: Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer’s disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer’s disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer’s disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.
Published Version: doi:10.1038/nature13163
Other Sources: http://www.researchgate.net/profile/Liviu_Aron/publication/261138227_REST_and_stress_resistance_in_ageing_and_Alzheimer%27s_disease/links/0a85e53658f93b972f000000
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34605059
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