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.

Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis / C. Dianzani, D. Vecchio, N. Clemente, A. Chiocchetti, F. Martinelli Boneschi, D. Galimberti, U. Dianzani, C. Comi, M. Mishto, J. Liepe. - In: CELLS. - ISSN 2073-4409. - 8:3(2019 Mar 20). [10.3390/cells8030262]

Untangling Extracellular Proteasome-Osteopontin Circuit Dynamics in Multiple Sclerosis

F. Martinelli Boneschi;D. Galimberti;
2019

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.
chemotaxis; computational modelling; immunoproteasome; system biology
Settore BIO/13 - Biologia Applicata
20-mar-2019
Article (author)
File in questo prodotto:
File Dimensione Formato  
Dianzani et al.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 3.53 MB
Formato Adobe PDF
3.53 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/653170
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact