Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer's disease-associated genes.
Alzheimer’s disease
Drosophila
GWAS
lipid droplet
peroxidated lipid transfer
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
28 12 2021
28 12 2021
Historique:
accepted:
11
11
2021
entrez:
24
12
2021
pubmed:
25
12
2021
medline:
12
2
2022
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 34949639
pii: 2112095118
doi: 10.1073/pnas.2112095118
pmc: PMC8719885
pii:
doi:
Substances chimiques
Neuroprotective Agents
0
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : U01 AG072439
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007526
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD083092
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS043124
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG073260
Pays : United States
Organisme : NIH HHS
ID : R24 OD022005
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103555
Pays : United States
Déclaration de conflit d'intérêts
Competing interest statement: J.O.J. is the President and CEO of Artery Therapeutics, Inc. and part owner of a patent of the peptide used in this work (Patent WO2014144708A1).
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