PXD046040

PXD046040 is an original dataset announced via ProteomeXchange.

Title	INPP5D regulates inflammasome activation in human microglia
Description	Microglia and neuroinflammation play an important role in the development and progression of Alzheimer’s disease (AD). Inositol polyphosphate-5-phosphatase D (INPP5D) is a myeloid-expressed gene genetically-associated with AD. Through unbiased analyses of RNA and protein profiles in INPP5D-disrupted iPSC-derived human microglia, we find that reduction in INPP5D activity is associated with molecular profiles consistent with disrupted autophagy and inflammasome activation. These findings are validated through targeted pharmacological experiments which demonstrate that reduced INPP5D activity induces the formation of the NLRP3 inflammasome, cleavage of CASP1, and secretion of IL-1 and IL-18. Further, in-depth analyses of human brain tissue across hundreds of individuals using a multi-analytic approach provides evidence that a reduction in function of INPP5D in microglia results in inflammasome activation in AD. These findings provide insights into the molecular mechanisms underlying microglia-mediated processes in AD and highlight the inflammasome as a potential therapeutic target for modulating INPP5D-mediated vulnerability to AD.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:27:27.939.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duc Duong
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-10 12:26:16	ID requested
1	2024-01-26 10:31:58	announced
⏵ 2	2024-10-22 06:27:28	announced	2024-10-22: Updated project metadata.

Chou V, Pearse RV, Aylward AJ, Ashour N, Taga M, Terzioglu G, Fujita M, Fancher SB, Sigalov A, Benoit CR, Lee H, Lam M, Seyfried NT, Bennett DA, De Jager PL, Menon V, Young-Pearse TL, INPP5D regulates inflammasome activation in human microglia. Nat Commun, 14(1):7552(2023) [pubmed]

10.1038/s41467-023-42819-w;

submitter keyword: LC-MS/MS, Alzheimer's, INPP5D

Tracy Young-Pearse
contact affiliation	Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
contact email	tpearse@bwh.harvard.edu
lab head
Duc Duong
contact affiliation	Center of Neurodegenerative Diseases
contact email	dduong@emory.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD046040

PRIDE project URI

• PRIDE
  1. PXD046040
     1. Label: PRIDE project
     2. Name: INPP5D regulates inflammasome activation in human microglia