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ABeta-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer's disease
- ABeta-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer's disease
- 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
- Molecular Neurodegeneration, 10
- Article Type
- Alzheimer' s Disease (AD); Amyloid-Beta (ABeta); Amyloid Beta Protein; Animal Experiment; Animal Model; Behavior Disorder; BMAL1 (Aryl Hydrocarbon Receptor Nuclear Translocator-Like); Body Temperature; Carboxy Terminal Sequence; CBP (Creb-Binding Protein); Circadian Rhythm; Circadian Rhythm Sleep Disorder; Controlled Study; Cyclic AMP Responsive Element Binding Protein Binding Protein; Genetic Transfection; Human; Male; Molecular Clock; Molecular Interaction; Mouse; Mus; Nerve Cell Adhesion Molecule; Non-Human; Oscillation; PER2 Protein; Promoter Region; Protein BMAL1; Protein Degradation; Protein Expression; Protein Interaction; Regulatory Mechanism; Reporter Gene; Sleep Waking Cycle; Sumoylation; Transcription Factor Clock
- 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.
- BioMed Central Ltd.
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- Brain and Cognitive SciencesETC1. Journal Articles
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