PXD056276

PXD056276 is an original dataset announced via ProteomeXchange.

Title	SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain
Description	A role for the type I transmembrane trafficking receptor SORLA in reducing Aβ levels has been well-established, however, virtually nothing is known with respect to whether and how SORLA can potentially affect tau pathology. Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q. snRNAseq analysis reveals suppression of PS19-dependent signatures with SORLA upregulation, including proinflammatory induction of Plxnb1/Plxnb2 in glial cell types. PlxnB1/B2 expression as well as other neuroinflammatory features are exacerbated in PS19 hippocampus with SORLA deletion. Together, these results implicate a global role for SORLA in neuroprotection from tau toxicity in PS19 mouse brain.
HostingRepository	PRIDE
AnnounceDate	2026-05-24
AnnouncementXML	Submission_2026-05-24_11:37:26.709.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Timothy Huang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-25 21:26:52	ID requested
⏵ 1	2026-05-24 11:37:27	announced

Dataset with its publication pending

submitter keyword: tauopathy, Alzheimer’s disease, tau, Plexin, semaphorin,SORLA, tau pathology

Timothy Y. Huang
contact affiliation	Degenerative Diseases Program, Center for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute
contact email	thuang@sbpdiscovery.org
lab head
Timothy Huang
contact affiliation	Sanford Burnham Prebys Medical Discovery Institute
contact email	huanglab.geo@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056276
     1. Label: PRIDE project
     2. Name: SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain