PXD045108

PXD045108 is an original dataset announced via ProteomeXchange.

Title	Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and direct anti-demyelination
Description	Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system (CNS). Ursolic acid (UA) can be used in the MS treatment with anti-inflammatory and neuroprotective activities. However, UA is insoluble in water, which may affect its medication effectiveness. In this study, we evaluated the pharmacological effects of UAOS-Na, a water-soluble UA derivative, on experimental autoimmune encephalomyelitis (EAE) mouse, explored its underlying mechanism, and verified the mechanism by in vitro and in vivo experiments. As we expected, UAOS-Na (30 mg/kg/d) delayed the onset time of EAE from 11.78 days post immunization (dpi) to 14.33 dpi, reduced the incidence from 90.0% to 42.9%, and was more effective than UA. UAOS-Na (60 mg/kg/d) significantly decreased the serum levels of IFN-γ, IL-17A, TNF-α and IL-6, reduced the mononuclear cell infiltration of spinal cord, and inhibited the overexpression of key transcription factors T-bet and ROR-γt of EAE mouse spinal cord and spleen. In addition, UAOS-Na attenuated demyelination and astrogliosis in the CNS of EAE and Cuprizone-induced mice. Mechanically, proteomics showed that 217 differential expression proteins (DEPs) were enriched and 215 were upregulated in EAE mice. After UAOS-Na treatment, 52 DEPs were enriched and 49 were downregulated, and these DEPs were markedly enriched in inositol phosphate metabolism, calcium, sphingolipid, cAMP, and antigen processing and presentation (APP) signaling pathways. Among them, there were few studies on APP signaling pathway related with MS. Therefore, we further investigated the effect of UAOS-Na on APP signaling pathway and found that UAOS-Na downregulated the protein levels of Tapbp and H2-T23 in MHC-I antigen presentation pathway and decreased the proliferation of splenic CD8 T cells, thereby inhibiting the CNS infiltration of CD8 T cells. Together, our findings demonstrated that UAOS-Na have both direct anti-demyelination and anti-inflammation effects. And it could reduce the inflammation of MS by downregulating the expression of Tapbp and H2-T23 in the MHC-I antigen presentation pathway.
HostingRepository	PRIDE
AnnounceDate	2023-11-30
AnnouncementXML	Submission_2023-11-30_03:55:29.752.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gao Yuan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-05 07:17:43	ID requested
⏵ 1	2023-11-30 03:55:30	announced

10.3389/FNEUR.2023.1269862;

submitter keyword: multiple sclerosis

experimental autoimmune encephalomyelitis

ursolic acid

MHC-I antigen presentation pathway

Tapbp

H2-T23

Wang Maolin
contact affiliation	Shanghai university of Traditional Chinese Medicine
contact email	17715702971@163.com
lab head
Gao Yuan
contact affiliation	Southwest Medical University
contact email	gaobokl@163.com
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/2023/11/PXD045108

PRIDE project URI

• PRIDE
  1. PXD045108
     1. Label: PRIDE project
     2. Name: Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and direct anti-demyelination