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The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in A beta generation

Blondrath, K; Steel, JH; Katsouri, L; Ries, M; Parker, MG; Christian, M; Sastre, M; (2016) The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in A beta generation. Neurobiology of Aging , 47 pp. 180-191. 10.1016/j.neurobiolaging.2016.08.003. Green open access

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Abstract

The receptor interacting protein-140 (RIP140) is a cofactor for several nuclear receptors and has been involved in the regulation of metabolic and inflammatory genes. We hypothesize that RIP140 may also affect Aβ generation because it modulates the activity of transcription factors previously implicated in amyloid precursor protein (APP) processing, such as peroxisome proliferator-activated receptor-γ (PPARγ). We found that the levels of RIP140 are reduced in Alzheimer's disease (AD) postmortem brains compared with healthy controls. In addition, in situ hybridization experiments revealed that RIP140 expression is enriched in the same brain areas involved in AD pathology, such as cortex and hippocampus. Furthermore, we provide evidence using cell lines and genetically modified mice that RIP140 is able to modulate the transcription of certain genes involved in AD pathology, such as β-APP cleaving enzyme (BACE1) and GSK3. Consequently, we found that RIP140 overexpression reduced the generation of Aβ in a neuroblastoma cell line by decreasing the transcription of β-APP cleaving enzyme via a PPARγ–dependent mechanism. The results of this study therefore provide molecular insights into common signaling pathways linking metabolic disease with AD.

Type: Article
Title: The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in A beta generation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neurobiolaging.2016.08.003
Publisher version: http://doi.org/10.1016/j.neurobiolaging.2016.08.00...
Language: English
Additional information: © 2016 Elsevier Inc. All rights reserved. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Geriatrics & Gerontology, Neurosciences, Neurosciences & Neurology, PPAR gamma, Alzheimer's disease, RIP140, BACE1, GSK3, A beta, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, TRANSCRIPTIONAL COREPRESSOR RIP140, GLYCOGEN-SYNTHASE KINASE-3, AMYLOID PRECURSOR PROTEIN, PPAR-GAMMA, ALZHEIMERS-DISEASE, INSULIN-RESISTANCE, OXIDATIVE-METABOLISM, DIABETES-MELLITUS, SIGNALING PATHWAY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre
URI: http://discovery.ucl.ac.uk/id/eprint/10035015
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