title: The Brain Proteome of the Ubiquitin Ligase Peli1 Knock-Out Mouse during Experimental Autoimmune Encephalomyelitis.
abstract: The ubiquitin ligasePeli1has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis,Peli1knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia,Peli1expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes ofPeli1knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak. Brain samples from the frontal hemisphere, peripheral from the extensive inflammatory foci, were analyzed using TMT-labeling of sample pools, and the discovered proteins were verified in individual mice using label-free proteomics. The greatest proteomic differences betweenPeli1knock-out and wild-type mice were observed at the disease peak. InPeli1knock-out a higher degree of antigen presentation, increased activity of adaptive and innate immune cells and alterations to proteins involved in iron metabolism were observed during experimental autoimmune encephalomyelitis. These results unravel global effects to the brain proteome when abrogatingPeli1expression, underlining the importance ofPeli1as a regulator of the immune response also peripheral to inflammatory foci during experimental autoimmune encephalomyelitis. The proteomics data is available in PRIDE with accession PXD003710.
authors.affiliation: Proteomics Unit, Department of Biomedicine, University of Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen Norway.
authors.forename: Ragnhild Reehorst
authors.initials: RR
authors.lastname: Lereim
authors.affiliation: Proteomics Unit, Department of Biomedicine, University of Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen Norway.
authors.forename: Eystein
authors.initials: E
authors.lastname: Oveland
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University, Shanghai 200031, China.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen Norway; Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Torkildsen
authors.affiliation: Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen Norway; Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stig
authors.initials: S
authors.lastname: Wergeland
authors.affiliation: Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen Norway; Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
authors.affiliation: Proteomics Unit, Department of Biomedicine, University of Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen Norway; Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Frode S
authors.initials: FS
authors.lastname: Berven
keywords: Brain; Experimental autoimmune encephalomyelitis (EAE); Label-free proteomics; Multiple sclerosis; Peli1 knock-out; TMT-labeling proteomics