PXD027152 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | High inflammatory activity in patients with multiple sclerosis induces a specific astrocyte reactive state that drives non-cell-autonomous neuronal degenerationHigh inflammatory activity in patients with multiple sclerosis induces a specific astrocyte reactive state that drives non-cell-autonomous neuronal degeneration |
Description | Astrocytes contribute to the pathogenesis of multiple sclerosis (MS); however, the mechanisms underlying the regulation of astrocytic responses remain unknown. Here we report an exhaustive molecular and functional characterization of astrocyte reactivity following exposure to cerebrospinal fluid (CSF) from MS patients classified according to the degree of inflammatory activity. We showed that mouse astrocytes exposed to CSF from patients with high inflammatory activity (MS-High) exhibited a specific pro-inflammatory reactive state that was characterized by enhanced NF-kB signalling. This reactive astrocyte state conferred a dysfunctional response through an altered pro-inflammatory secretome that drove neuronal dysfunction and impaired synaptic plasticity. SerpinE1 was identified as a potential downstream mediator of the non-cell-autonomous toxic effect on neuronal function based on its significant up-regulation in secretomes from astrocytes exposed to CSF from MS-high patients. Further, we identified chitinase 3-like 1 as a potential upstream modulator of astrocyte reactivity via activation of NF-kB signalling based on its significantly increased levels in the CSF from MS-High patients. Taken together our findings indicate that the inflammatory microenvironment in the central nervous system of MS patients can induce specific reactive astrocyte states that trigger neuronal degeneration and may ultimately contribute to disease progression. |
HostingRepository | PRIDE |
AnnounceDate | 2022-06-23 |
AnnouncementXML | Submission_2022-06-23_03:53:19.864.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Eva Borràs |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-07-07 02:32:45 | ID requested | |
⏵ 1 | 2022-06-23 03:53:20 | announced | |
Publication List
Matute-Blanch C, Brito V, Midaglia L, Villar LM, Garcia-Diaz Barriga G, Guzman de la Fuente A, Borr, á, s E, Fern, á, ndez-Garc, í, a S, Calvo-Barreiro L, Miguez A, Costa-Frossard L, Pinteac R, Sabid, ó E, Alberch J, Fitzgerald DC, Montalban X, Comabella M, Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage. Clin Transl Med, 12(5):e837(2022) [pubmed] |
Keyword List
submitter keyword: Multiple Sclerosis, proteomics, astrocytes |
Contact List
Eduard Sabido |
contact affiliation | CRG, UPF |
contact email | eduard.sabido@crg.eu |
lab head | |
Eva Borràs |
contact affiliation | UPF |
contact email | eva.borras@upf.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD027152
- Label: PRIDE project
- Name: High inflammatory activity in patients with multiple sclerosis induces a specific astrocyte reactive state that drives non-cell-autonomous neuronal degenerationHigh inflammatory activity in patients with multiple sclerosis induces a specific astrocyte reactive state that drives non-cell-autonomous neuronal degeneration