⮝ Full datasets listing
PXD062821
PXD062821 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Pingping_2025_NC_N-acetyl-l-leucine_PD |
| Description | Abstract N-acetyl-L-leucine (NALL), a derivative of the branched-chain amino acid leucine, has shown therapeutic potential in neurodegenerative diseases, including in prodromal stages of Parkinson s disease (PD). However, the mechanism of its protective effects has been largely unknown. Using discovery-based proteomics, we found that treatment with NALL led to upregulation of lysosomal, mitochondrial, and synaptic proteins in PD patient-derived dopaminergic neurons. NALL reduced levels of pathological pS129-alpha-synuclein in dopaminergic neurons from patients harboring GBA1 or LRRK2 mutations. This decrease in pS129-syn was dependent on serine protease HTRA1 that was induced by NALL treatment of dopaminergic neurons. NALL also upregulated expression of wild-type parkin in both GBA1 and LRRK2 mutant neurons, leading to an increase in functional dopamine transporter and synaptic membrane-associated synaptojanin-1, suggesting improved synaptic function. Furthermore, NALL treatment of mutant LRRK2R1441C knock-in mice led to decreased pS129-alpha-synuclein, increased parkin and improved dopamine-dependent motor learning deficits. These findings highlight the therapeutic potential of NALL in PD by its protective effects on alpha-synuclein pathology and synaptic function in vulnerable dopaminergic neurons. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-12-22 |
| AnnouncementXML | Submission_2025-12-22_10:43:03.532.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 | TMTpro |
| Instrument | Orbitrap Ascend |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-04-10 12:19:33 | ID requested | |
| ⏵ 1 | 2025-12-22 10:43:04 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: NALL, synuclein, synaptic function, PD, DatasetType:Proteomics |
Contact List
| jeffrey Savas | |
|---|---|
| contact affiliation | Northwestern University Feinberg |
| contact email | jeffrey.savas@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/MSV000097594/ |
