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

Title
ABeta-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer's disease
Authors
Song, H[Song, Hyundong]Moon, M[Moon, Minho]Choe, HK[Choe, Han Kyoung]Han, DH[Han, Dong-Hee]Jang, C[Jang, Changhwan]Kim, A[Kim, Ahbin]Cho, S[Cho, Sehyung]Kim, K[Kim, Kyungjin]Mook-Jung, I[Mook-Jung, Inhee]
DGIST Authors
Kim, K[Kim, Kyungjin]
Issue Date
2015-03-19
Citation
Molecular Neurodegeneration, 10
Type
Article
Article Type
Article
Keywords
Alzheimer&aposs Disease (AD)Amyloid-Beta (ABeta)Amyloid Beta ProteinAnimal ExperimentAnimal ModelBehavior DisorderBMAL1 (Aryl Hydrocarbon Receptor Nuclear Translocator-Like)Body TemperatureCarboxy Terminal SequenceCBP (Creb-Binding Protein)Circadian RhythmCircadian Rhythm Sleep DisorderControlled StudyCyclic AMP Responsive Element Binding Protein Binding ProteinGenetic TransfectionHumanMaleMolecular ClockMolecular InteractionMouseMusNerve Cell Adhesion MoleculeNon-HumanOscillationPER2 ProteinPromoter RegionProtein BMAL1Protein DegradationProtein ExpressionProtein InteractionRegulatory MechanismReporter GeneSleep Waking CycleSumoylationTranscription Factor Clock
ISSN
1750-1326
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. © 2015 Song et al.; licensee BioMed Central.
URI
http://hdl.handle.net/20.500.11750/2607
DOI
10.1186/s13024-015-0007-x
Publisher
BioMed Central Ltd.
Files:
There are no files associated with this item.
Collection:
Department of Brain and Cognitive SciencesETC1. Journal Articles


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