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

Blondrath, K, Steel, JH, Katsouri, L, Ries, M, Parker, MG, Christian, M ORCID: https://orcid.org/0000-0002-1616-4179 and Sastre, M, 2016. The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in Aβ generation. Neurobiology of Aging, 47, pp. 180-191. ISSN 0197-4580

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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.

Item Type:	Journal article
Publication Title:	Neurobiology of Aging
Creators:	Blondrath, K., Steel, J.H., Katsouri, L., Ries, M., Parker, M.G., Christian, M. and Sastre, M.
Publisher:	Elsevier
Date:	November 2016
Volume:	47
ISSN:	0197-4580
Identifiers:	Number Type 10.1016/j.neurobiolaging.2016.08.003 DOI S0197458016301701 Publisher Item Identifier
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	09 Aug 2019 10:03
Last Modified:	09 Aug 2019 10:03
URI:	https://irep.ntu.ac.uk/id/eprint/37205

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