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PXD027152

PXD027152 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHigh 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
DescriptionAstrocytes 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.
HostingRepositoryPRIDE
AnnounceDate2022-06-23
AnnouncementXMLSubmission_2022-06-23_03:53:19.864.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEva Borràs
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-07-07 02:32:45ID requested
12022-06-23 03:53:20announced
Publication List
Matute-Blanch C, Brito V, Midaglia L, Villar LM, Garcia-Diaz Barriga G, Guzman de la Fuente A, Borrás E, Fernández-García S, Calvo-Barreiro L, Miguez A, Costa-Frossard L, Pinteac R, Sabidó 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 affiliationCRG, UPF
contact emaileduard.sabido@crg.eu
lab head
Eva Borràs
contact affiliationUPF
contact emaileva.borras@upf.edu
dataset submitter
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Dataset FTP location
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