Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/91674
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dc.contributorDepartment of Health Technology and Informatics-
dc.creatorChow, HM-
dc.creatorSun, JKL-
dc.creatorHart, RP-
dc.creatorCheng, KKY-
dc.creatorHung, CHL-
dc.creatorLau, TM-
dc.creatorKwan, KM-
dc.date.accessioned2021-11-24T06:07:36Z-
dc.date.available2021-11-24T06:07:36Z-
dc.identifier.issn2198-3844-
dc.identifier.urihttp://hdl.handle.net/10397/91674-
dc.language.isoenen_US
dc.publisherWiley-VCHen_US
dc.rights© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.en_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction inany medium, provided the original work is properly cited.en_US
dc.rightsThe following publication Chow, H. M., Sun, J. K. L., Hart, R. P., Cheng, K. K. Y., Hung, C. H., Lau, T. M., & Kwan, K. M. (2021). Low‐Density Lipoprotein Receptor‐Related Protein 6 Cell Surface Availability Regulates Fuel Metabolism in Astrocytes. Advanced Science, 8(16), 2004993 is available at https://doi.org/10.1002/advs.202004993en_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectAmino acid metabolismen_US
dc.subjectAstrocyteen_US
dc.subjectMetabolic reprogrammingen_US
dc.subjectWnt signalingen_US
dc.titleLow-density lipoprotein receptor-related protein 6 cell surface availability regulates fuel metabolism in astrocytesen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.doi10.1002/advs.202004993-
dcterms.abstractEarly changes in astrocyte energy metabolism are associated with late-onset Alzheimer's disease (LOAD), but the underlying mechanism remains elusive. A previous study suggested an association between a synonymous SNP (rs1012672, C -> T) in LRP6 gene and LOAD; and that is indeed correlated with diminished LRP6 gene expression in the frontal cortex region. The authors show that LRP6 is a unique Wnt coreceptor on astrocytes, serving as a bimodal switch that modulates their metabolic landscapes. The Wnt-LRP6 mediated mTOR-AKT axis is essential for sustaining glucose metabolism. In its absence, Wnt switches to activate the LRP6-independent Ca2+-PKC-NFAT axis, resulting in a transcription network that favors glutamine and branched chain amino acids (BCAAs) catabolism over glucose metabolism. Exhaustion of these raw materials essential for neurotransmitter biosynthesis and recycling results in compromised synaptic, cognitive, and memory functions; priming for early changes that are frequently found in LOAD. The authors also highlight that intranasal supplementation of glutamine and BCAAs is effective in preserving neuronal integrity and brain functions, proposing a nutrient-based method for delaying cognitive and memory decline when LRP6 cell surface levels and functions are suboptimal.-
dcterms.accessRightsopen accessen_US
dcterms.bibliographicCitationAdvanced science, 18 Aug. 2021, 2004993, https://doi.org/10.1002/advs.202004993-
dcterms.isPartOfAdvanced science-
dcterms.issued2021-08-
dc.identifier.isiWOS:000667111300001-
dc.identifier.pmid34180138-
dc.identifier.artn2004993-
dc.description.validate202111 bchy-
dc.description.oaVersion of Recorden_US
dc.identifier.FolderNumberOA_Scopus/WOSen_US
dc.description.pubStatusEarly releaseen_US
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