PXD081397-1

PXD081397 is an original dataset announced via ProteomeXchange.

Title	Huntington’s disease vasculopathy is barrier-type-selective and arteriolar-dominant with spatially-coupled astrogliosis and reversible by S1pr1 stimulation
Description	Brain vascular barriers are dysfunctional in many neurological disorders, including Huntington’s disease (HD), but which vessels are affected and how remains unclear. Using in vivo two-photon microscopy in R6/2 HD-model mice, we reveal a striking divergence in barrier dysfunction. Surface vessels of the blood-cerebrospinal fluid barrier (BCSFB) drive pathology by paracellular leakage, while the blood-brain barrier (BBB) of parenchymal vessels exhibited increased vesicular transport and adsorptive-mediated transcytosis (AMT), with arterioles representing the most critically impacted vascular segment. The pathology of both barriers was congruent with astrocyte activation localized to affected vessels in R6/2 mice, as well as in post-mortem HD human brains. Sphingosine-1-phosphate receptor 1 (S1pr1) agonist treatment reversed BCSFB leakage but only partially restored BBB function, selectively reducing AMT in arterioles, with no effect in capillaries and venules. These findings redefine HD vascular pathology, demonstrating heterogeneous, vessel-type-specific barrier failure beyond generalized "disruption," uncovering mechanistic vulnerabilities and the therapeutic potential of S1pr1 modulation.
HostingRepository	PRIDE
AnnounceDate	2026-08-14
AnnouncementXML	Submission_2026-08-14_02:02:02.835.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Niels Henning Skotte
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-21 09:37:28	ID requested
⏵ 1	2026-08-14 02:02:03	announced

Dataset with its publication pending

submitter keyword: Blood-brain barrier,Huntington's Disease, Plasma, Mouse, CSF, Orbitrap Astral, Proteomics

Niels Skotte
contact affiliation	Department for Drug Design and Pharmacology, University of Copenhagen
contact email	niels.skotte@sund.ku.dk
lab head
Niels Henning Skotte
contact affiliation	University of Copenhagen
contact email	niels.skotte@sund.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD081397
     1. Label: PRIDE project
     2. Name: Huntington’s disease vasculopathy is barrier-type-selective and arteriolar-dominant with spatially-coupled astrogliosis and reversible by S1pr1 stimulation