Low-Density Lipoprotein Receptor-Related Protein 6 Cell Surface Availability Regulates Fuel Metabolism in Astrocytes.

ABSTRACT: Early 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 metabo

SUBMITTER: Chow HM 

PROVIDER: S-EPMC8373092 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature