⮝ Full datasets listing
PXD062090-1
PXD062090 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Macro_NN_2025_Pro-cognitive reshaping of neuronal dynamics by a human CSF-based factor |
| Description | Neuronal connection dysfunction is a convergent cause of cognitive deficits in mental disorders. Cognitive processes are finely regulated at the synaptic level by membrane proteins, some of which are shed and detectable in patients' cerebrospinal fluid (CSF). However, whether these soluble synaptic proteins can harnessed as innovative pro-cognitive factors to treat brain disorders remains unclear. Here, we use quantitative proteomics to identify shed synaptic proteins dysregulated in the CSF of subjects with schizophrenia (SCZ), a mental disorder characterized by cognitive and synaptic dysfunction. The level of a yet uncharacterized soluble form of the voltage-gated calcium channel auxiliary subunit, alpha2delta-1, is robustly reduced in SCZ CSF. Remarkably, soluble alpha2delta-1 is convergently downregulated across several brain disorder CSF proteomes. We show that the brain releases soluble alpha2delta-1 in an activity-dependent manner, which can reorganize neuronal network dynamics by binding to synaptic targets and promoting inhibitory neuron plasticity. A single brain injection of a synthetic soluble alpha2delta-1 improved interneuron and cognitive deficits in a mutant mouse model of SCZ and cortical dysfunction. These findings underscore the potential of shed synaptic proteins as novel therapeutic agents capable of enhancing brain function in diverse brain disorders characterized by cognitive impairment. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-03-10 |
| AnnouncementXML | Submission_2026-03-10_11:06:15.523.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Jeffrey N. Savas |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | unknown modification; Carbamidomethyl |
| Instrument | Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-03-20 15:54:50 | ID requested | |
| ⏵ 1 | 2026-03-10 11:06:16 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Schizophrenia, cerebrospinal fluid, Cacna2d1, cognition, synapses, DatasetType:Proteomics |
Contact List
| Peter Penzes | |
|---|---|
| contact affiliation | Northwestern University, Feinberg School of Medicine |
| contact email | p-penzes@northwestern.edu |
| lab head | |
| Jeffrey N. Savas | |
| contact affiliation | Northwestern University |
| contact email | jeffrey.savas@northwestern.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive-ftp.ucsd.edu/v09/MSV000097391/ |
