Brain-derived immunoproteasome generates increased amounts of encephalitogenic MBP peptide epitopeстатьяТезисы
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 января 2019 г.
Аннотация:DOI:10.1111/febs.12340
# SW03.S15–4
Triggering of autoimmune diseases by autoantigens is poorly
understood. One of the crucial steps in antigen presentation on
MHC I is degradation of antigenic protein by proteasome. We
studied proteasome-mediated degradation of myelin basic protein
(MBP), one of major autoantigenes in multiple sclerosis and its
animal model, experimental autoimmune encephalomyelitis
(EAE). We have demonstrated a dramatic shift in the balance
between constitutive and immuno proteasomes in the CNS of
SJL mice with EAE, with immunoproteasome subunit LMP2
localized mainly in oligodendrocytes. Patterns of MBP degradation
by proteasome from brain of EAE mice and control nontreated
mice were compared by MS spectra using 16O/18O labeling
and isotope-labeled synthetic peptides. Elevated levels of immunoproteasome
in brain of mice with EAE result in an
increased production of several peptides, including peptide ENPVVHFF,
a part of encephalitogenic MBP region. Peptidyl epoxyketone
inhibitor of LMP2 immunoproteasome subunit affects
catalytic activity of brain-derived immunoproteasome in vitro
and ameliorates ongoing demyelination in vivo, suggesting a
novel treatment modality of autoimmune neurological diseases.