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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2015

Open Access 01-12-2015 | Research article

Aβ-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer’s disease

Authors: Hyundong Song, Minho Moon, Han Kyoung Choe, Dong-Hee Han, Changhwan Jang, Ahbin Kim, Sehyung Cho, Kyungjin Kim, Inhee Mook-Jung

Published in: Molecular Neurodegeneration | Issue 1/2015

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Abstract

Background

Patients with Alzheimer’s disease (AD) frequently experience disruption of their circadian rhythms, but whether and how circadian clock molecules are perturbed by AD remains unknown. AD is an age-related neurological disorder and amyloid-β (Aβ) is one of major causative molecules in the pathogenesis of AD.

Results

In this study, we investigated the role of Aβ in the regulation of clock molecules and circadian rhythm using an AD mouse model. These mice exhibited altered circadian behavior, and altered expression patterns of the circadian clock genes, Bmal1 and Per2. Using cultured cells, we showed that Aβ induces post-translational degradation of the circadian clock regulator CBP, as well as the transcription factor BMAL1, which forms a complex with the master circadian transcription factor CLOCK. Aβ-induced degradation of BMAL1 and CBP correlated with the reduced binding of transcription factors to the Per2 promoter, which in turn resulted in disruptions to PER2 protein expression and the oscillation of Per2 mRNA levels.

Conclusions

Our results elucidate the underlying mechanisms for disrupted circadian rhythm in AD.
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Metadata
Title
Aβ-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer’s disease
Authors
Hyundong Song
Minho Moon
Han Kyoung Choe
Dong-Hee Han
Changhwan Jang
Ahbin Kim
Sehyung Cho
Kyungjin Kim
Inhee Mook-Jung
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2015
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-015-0007-x

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