PXD043877

PXD043877 is an original dataset announced via ProteomeXchange.

Title	Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy
Description	Alzheimer’s disease is associated with disrupted circadian rhythms and clock gene expression. REV-ERBα (Nr1d1) is a circadian transcriptional repressor involved in the regulation of lipid metabolism and macrophage function. While global REV-ERBα deletion increases microglial activation and mitigates amyloid plaque formation, the cell-autonomous effects of microglial REV-ERBα deletion in healthy brain and in tauopathy are unexplored. Here, we show that microglial REV-ERBα deficient enhances inflammatory signaling, disrupts lipid metabolism, and causes lipid droplet (LD) accumulation specifically in male microglia. Inflammation and LD accumulation combine to inhibit microglial tau phagocytosis, which can be partially rescued by blockage of lipid droplet formation. Microglial REV-ERBα deletion exacerbates tau aggregation and neuroinflammation in P301S and AAV-P301L tauopathy models in male, but not female mice. These data demonstrate the importance of microglial lipid droplets in tau accumulation and reveal REV-ERBα as a therapeutically accessible, sex-dependent regulator of microglial inflammatory signaling, lipid metabolism, and tauopathy.
HostingRepository	PRIDE
AnnounceDate	2023-08-09
AnnouncementXML	Submission_2023-08-09_14:29:43.148.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043877
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	MinsooSon
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-18 19:21:24	ID requested
⏵ 1	2023-08-09 14:29:43	announced

10.6019/PXD043877;

submitter keyword: Alzheimer’s disease, Tau,Circadian, Microglia, Rev-erbα

ErikMusiek
contact affiliation	Department of Neurology and Center On Biological Rhythms And Sleep, Washington University in St. Louis School of Medicine, St. Louis, MO USA
contact email	musieke@wustl.edu
lab head
MinsooSon
contact affiliation	WashU
contact email	son.m@wustl.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043877
     1. Label: PRIDE project
     2. Name: Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy