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PXD061834

PXD061834 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePharmacological inhibition of PSPH reduces serine levels and epileptic seizures
DescriptionTemporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy. Lowering the levels of N-methyl-D-aspartate receptor (NMDAR) ligands has been suggested as a promising therapeutic strategy for TLE. D-serine gates synaptic NMDARs in the hippocampus, but the effect of D-serine on seizure activity remains poorly understood. Here, we show that serine levels in the hippocampus were increased in patients with TLE and in a mouse model of TLE. Eliminating D-serine or blocking its binding with NMDARs suppressed seizures in mouse models. Astrocyte-derived L-serine was found to regulate interstitial D-serine levels and seizure activity through a process controlled by phosphoserine phosphatase (PSPH). We identified a potent PSPH inhibitor, Z218484536, and found that its systemic administration reduced spontaneous epileptic discharges in mouse and cynomolgus monkey models of TLE. Overall, these results indicate that PSPH is a promising therapeutic target for TLE and support further preclinical studies of Z
HostingRepositoryiProX
AnnounceDate2025-03-14
AnnouncementXMLSubmission_2025-03-14_04:54:36.389.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYanbing Wang
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-03-14 04:45:16ID requested
12025-03-14 04:54:37announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Temporal lobe epilepsy, NMDAR, PSPH, D-serine
Contact List
Yanbing Wang
contact affiliationChinese Academy of Medical Sciences and Peking Union Medical College
contact emailw18634306858@163.com
lab head
Yanbing Wang
contact affiliationChinese Academy of Medical Sciences and Peking Union Medical College
contact emailw18634306858@163.com
dataset submitter
Full Dataset Link List
iProX dataset URI