PXD061835
PXD061835 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Pharmacological inhibition of PSPH reduces serine levels and epileptic seizures-Phosphoproteomics |
| 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 Z218484536. |
| HostingRepository | iProX |
| AnnounceDate | 2025-03-14 |
| AnnouncementXML | Submission_2025-03-14_04:57:09.754.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 | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-03-14 04:56:08 | ID requested | |
| ⏵ 1 | 2025-03-14 04:57:10 | 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 |
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