Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease

Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, Chungcheongnam-do, Korea

Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan 31538, Chungcheongnam-do, Korea

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(21), 7862; https://doi.org/10.3390/ijms21217862

Received: 5 October 2020 / Revised: 20 October 2020 / Accepted: 22 October 2020 / Published: 23 October 2020

(This article belongs to the Special Issue Neurogenesis and Neural Plasticity)

View Full-Text Download PDF

Browse Figures

Review Reports Citation Export

Abstract

Altered glucose metabolism has been implicated in the pathogenesis of Alzheimer’s disease (AD). Aerobic glycolysis from astrocytes is a critical metabolic pathway for brain energy metabolism. Disturbances of circadian rhythm have been associated with AD. While the role of circadian locomotor output cycles kaput (CLOCK) and brain muscle ARNT-like1 (BMAL1), the major components in the regulation of circadian rhythm, has been identified in the brain, the mechanism by which CLOCK and BMAL1 regulates the dysfunction of astrocytes in AD remains unclear. Here, we show that the protein levels of CLOCK and BMAL1 are significantly elevated in impaired astrocytes of cerebral cortex from patients with AD. We demonstrate that the over-expression of CLOCK and BMAL1 significantly suppresses aerobic glycolysis and lactate production by the reduction in hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) protein levels in human astrocytes. Moreover, the elevation of CLOCK and BMAL1 induces functional impairment by the suppression of glial fibrillary acidic protein (GFAP)-positive filaments in human astrocytes. Furthermore, the elevation of CLOCK and BMAL1 promotes cytotoxicity by the activation of caspase-3-dependent apoptosis in human astrocytes. These results suggest that the elevation of CLOCK and BMAL1 contributes to the impairment of astrocytes by inhibition of aerobic glycolysis in AD. View Full-Text

Keywords: CLOCK; BMAL1; aerobic glycolysis; astrocytes; Alzheimer’s disease

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
PDF-Document (PDF, 3499 KiB)

Share and Cite

MDPI and ACS Style

Yoo, I.D.; Park, M.W.; Cha, H.W.; Yoon, S.; Boonpraman, N.; Yi, S.S.; Moon, J.-S. Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 7862. https://doi.org/10.3390/ijms21217862

AMA Style

Yoo ID, Park MW, Cha HW, Yoon S, Boonpraman N, Yi SS, Moon J-S. Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease. International Journal of Molecular Sciences. 2020; 21(21):7862. https://doi.org/10.3390/ijms21217862

Chicago/Turabian Style

Yoo, Ik D., Min W. Park, Hyeon W. Cha, Sunmi Yoon, Napissara Boonpraman, Sun S. Yi, and Jong-Seok Moon. 2020. "Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease" International Journal of Molecular Sciences 21, no. 21: 7862. https://doi.org/10.3390/ijms21217862

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI