The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in Aβ generation
File(s)
Accepted version
Author(s)
Type
Journal Article
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 APP processing, such as PPARγ. We found that the levels of RIP140 are reduced in AD post-mortem 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 BACE1 and GSK3. Consequently, we found that RIP140 overexpression reduced the generation of Aβ in a neuroblastoma cell line by decreasing the transcription of BACE1 via a PPARγ-dependent mechanism. The results of this study therefore provide molecular insights into common signalling pathways linking metabolic disease with AD.
Date Issued
2016-08-12
Date Acceptance
2016-08-04
Citation
Neurobiology of Aging, 2016, 47, pp.180-191
ISSN
1558-1497
Publisher
Elsevier
Start Page
180
End Page
191
Journal / Book Title
Neurobiology of Aging
Volume
47
Copyright Statement
© 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Alzheimer's Research UK (ARUK)
Grant Number
ART/PhD2011-16
Subjects
Alzheimer's disease
Aβ
BACE1
GSK3
PPARγ
RIP140
Neurology & Neurosurgery
1103 Clinical Sciences
1109 Neurosciences
Publication Status
Published