PXD035149-1

PXD035149 is an original dataset announced via ProteomeXchange.

Title	ORP6 regulates astrocytic cholesterol metabolism and brain Aβ deposition
Description	The mammalian brain is the most cholesterol-rich organ of the body, requiring in situ de novo cholesterol synthesis to meet this demand. Defects in brain cholesterol homeostasis are implicated in cognitive deficits related to aging and in neurodegenerative diseases, such as Alzheimer’s Disease (AD). Oxysterol-binding protein (OSBP)-related proteins (ORPs) are highly conserved cytosolic proteins that coordinate lipid homeostasis by regulating cell signaling, inter-organelle membrane contact sites and non-vesicular transport of cholesterol. Here, we show that ORP6 is highly expressed in the brain, where it exhibits spatial and cell-type specific expression. ORP6 expression is enriched in the hippocampus and caudal-putamen brain regions, specifically within neurons and astrocytes. ORP6 knockdown in astrocytes altered the expression of cholesterol biosynthesis, cholesterol efflux and cholesterol esterification genes, resulting in the accumulation of esterified cholesterol within cellular lipid droplets and reduced cholesterol efflux. Furthermore, ORP6 ablation in mice resulted in dysregulation of whole body lipid homeostasis, increased brain desmosterol and Aβ deposition, and cognitive impairment. Our findings highlight a critical role for ORP6 in brain cholesterol homeostasis and identify ORP6 as a potential novel target for the treatment of AD.
HostingRepository	PRIDE
AnnounceDate	2025-10-07
AnnouncementXML	Submission_2025-10-07_10:31:48.904.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rachel Nadeau
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-07 01:06:45	ID requested
⏵ 1	2025-10-07 10:31:49	announced

10.1016/j.jlr.2025.100868;

Kasongo AA, Vijithakumar V, Abd-Elrahman KS, Prabhune R, Gharibeh L, Nadeau R, Robillard I, Spring S, Robichaud S, Asif S, Gibbings D, Moore KJ, Sled JG, Ruiz M, Lavall, é, e-Adam M, Ferguson SSG, Lacoste B, Lagace DC, Ouimet M, production. J Lipid Res, 66(9):100868(2025) [pubmed]

submitter keyword: Mouse, Brain, Label-Free, HPLC-ESI-MS/MS

Mireille Ouimet
contact affiliation	Department of Biochemistry, Microbiology and Immunology, University of Ottawa; University of Ottawa Heart Institute
contact email	mireille.ouimet@uottawa.ca
lab head
Rachel Nadeau
contact affiliation	University of Ottawa
contact email	rnade046@uottawa.ca
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/2025/09/PXD035149

PRIDE project URI

• PRIDE
  1. PXD035149
     1. Label: PRIDE project
     2. Name: ORP6 regulates astrocytic cholesterol metabolism and brain Aβ deposition