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  Untangling extracellular proteasome-osteopontin circuit dynamics in multiple sclerosis.

Dianzani, C., Vecchio, D., Clemente, N., Chiocchetti, A., Boneschi, F. M., Galimberti, D., et al. (2019). Untangling extracellular proteasome-osteopontin circuit dynamics in multiple sclerosis. Cells, 8(3): 262. doi:10.3390/cells8030262.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-3A9B-E Version Permalink: http://hdl.handle.net/21.11116/0000-0003-3A9F-A
Genre: Journal Article

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 Creators:
Dianzani, C., Author
Vecchio, D., Author
Clemente, N., Author
Chiocchetti, A., Author
Boneschi, F. M., Author
Galimberti, D., Author
Dianzani, U., Author
Comi, C., Author
Mishto, M., Author
Liepe, J.1, Author              
Affiliations:
1Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_2466694              

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Free keywords: immunoproteasome; chemotaxis; computational modelling; system biology
 Abstract: The function of proteasomes in extracellular space is still largely unknown. The extracellular proteasome-osteopontin circuit has recently been hypothesized to be part of the inflammatory machinery regulating relapse/remission phase alternation in multiple sclerosis. However, it is still unclear what dynamics there are between the different elements of the circuit, what the role of proteasome isoforms is, and whether these inflammatory circuit dynamics are associated with the clinical severity of multiple sclerosis. To shed light on these aspects of this novel inflammatory circuit, we integrated in vitro proteasome isoform data, cell chemotaxis cell culture data, and clinical data of multiple sclerosis cohorts in a coherent computational inference framework. Thereby, we modeled extracellular osteopontin-proteasome circuit dynamics during relapse/remission alternation in multiple sclerosis. Applying this computational framework to a longitudinal study on single multiple sclerosis patients suggests a complex interaction between extracellular proteasome isoforms and osteopontin with potential clinical implications.

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Language(s): eng - English
 Dates: 2019-03-182019-03-20
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.3390/cells8030262
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Title: Cells
Source Genre: Journal
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Pages: 22 Volume / Issue: 8 (3) Sequence Number: 262 Start / End Page: - Identifier: -