PXD061834
PXD061834 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Pharmacological inhibition of PSPH reduces serine levels and epileptic seizures |
Description | Temporal 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 |
HostingRepository | iProX |
AnnounceDate | 2025-03-14 |
AnnouncementXML | Submission_2025-03-14_04:54:36.389.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Yanbing Wang |
SpeciesList | scientific name: Mus musculus; NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2025-03-14 04:45:16 | ID requested | |
⏵ 1 | 2025-03-14 04:54:37 | announced |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Temporal lobe epilepsy, NMDAR, PSPH, D-serine |
Contact List
Yanbing Wang | |
---|---|
contact affiliation | Chinese Academy of Medical Sciences and Peking Union Medical College |
contact email | w18634306858@163.com |
lab head | |
Yanbing Wang | |
contact affiliation | Chinese Academy of Medical Sciences and Peking Union Medical College |
contact email | w18634306858@163.com |
dataset submitter |
Full Dataset Link List
iProX dataset URI |