Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yoo, Ik Dong, Park, Min Woo, Cha, Hyeon Woo, Yoon, Sunmi, Boonpraman, Napissara, Yi, Sun Shin, Moon, Jong-Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660350/
https://www.ncbi.nlm.nih.gov/pubmed/33114015
http://dx.doi.org/10.3390/ijms21217862
_version_ 1783608989629546496
author Yoo, Ik Dong
Park, Min Woo
Cha, Hyeon Woo
Yoon, Sunmi
Boonpraman, Napissara
Yi, Sun Shin
Moon, Jong-Seok
author_facet Yoo, Ik Dong
Park, Min Woo
Cha, Hyeon Woo
Yoon, Sunmi
Boonpraman, Napissara
Yi, Sun Shin
Moon, Jong-Seok
author_sort Yoo, Ik Dong
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7660350
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76603502020-11-13 Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease Yoo, Ik Dong Park, Min Woo Cha, Hyeon Woo Yoon, Sunmi Boonpraman, Napissara Yi, Sun Shin Moon, Jong-Seok Int J Mol Sci Article 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. MDPI 2020-10-23 /pmc/articles/PMC7660350/ /pubmed/33114015 http://dx.doi.org/10.3390/ijms21217862 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoo, Ik Dong
Park, Min Woo
Cha, Hyeon Woo
Yoon, Sunmi
Boonpraman, Napissara
Yi, Sun Shin
Moon, Jong-Seok
Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease
title Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease
title_full Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease
title_fullStr Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease
title_full_unstemmed Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease
title_short Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease
title_sort elevated clock and bmal1 contribute to the impairment of aerobic glycolysis from astrocytes in alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660350/
https://www.ncbi.nlm.nih.gov/pubmed/33114015
http://dx.doi.org/10.3390/ijms21217862
work_keys_str_mv AT yooikdong elevatedclockandbmal1contributetotheimpairmentofaerobicglycolysisfromastrocytesinalzheimersdisease
AT parkminwoo elevatedclockandbmal1contributetotheimpairmentofaerobicglycolysisfromastrocytesinalzheimersdisease
AT chahyeonwoo elevatedclockandbmal1contributetotheimpairmentofaerobicglycolysisfromastrocytesinalzheimersdisease
AT yoonsunmi elevatedclockandbmal1contributetotheimpairmentofaerobicglycolysisfromastrocytesinalzheimersdisease
AT boonpramannapissara elevatedclockandbmal1contributetotheimpairmentofaerobicglycolysisfromastrocytesinalzheimersdisease
AT yisunshin elevatedclockandbmal1contributetotheimpairmentofaerobicglycolysisfromastrocytesinalzheimersdisease
AT moonjongseok elevatedclockandbmal1contributetotheimpairmentofaerobicglycolysisfromastrocytesinalzheimersdisease