Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer's disease-associated genes.

ABSTRACT: A growing list of Alzheimer's disease (AD) genetic risk factors is being identified, but the contribution of each variant to disease mechanism remains largely unknown. We have previously shown that elevated levels of reactive oxygen species (ROS) induces lipid synthesis in neurons leading to the sequestration of peroxidated lipids in glial lipid droplets (LD), delaying neurotoxicity. This neuron-to-glia lipid transport is APOD/E-dependent. To identify proteins that modulate these neuroprotective effects, we tested the role of AD risk genes in ROS-induced LD formation and demonstrate that several genes impact neuroprotective LD formation, including homologs of human ABCA1, ABCA7, VLDLR, VPS26, VPS35, AP2A, PICALM, and CD2AP Our data also show that ROS enhances Aβ42 phenotypes in flies and m

SUBMITTER: Moulton MJ 

PROVIDER: S-EPMC8719885 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature