Matvey E. Lukashev

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Inflammation and oxidative stress are thought to promote tissue damage in multiple sclerosis. Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for multiple sclerosis treatment. BG00012 is an oral formulation of dimethylfumarate. In a phase II multiple sclerosis trial, BG00012 demonstrated beneficial effects on(More)
The cytoplasmic domains of integrin beta subunits are essential for the function of integrins in cell adhesion and signaling. A chimera combining the transmembrane and cytoplasmic domains of the beta 1 integrin subunit with an irrelevant extracellular domain derived from L3T4 (murine CD4) was tested for its ability to interfere with integrin function.(More)
Oxidative stress is central to the pathology of several neurodegenerative diseases, including multiple sclerosis, and therapeutics designed to enhance antioxidant potential could have clinical value. The objective of this study was to characterize the potential direct neuroprotective effects of dimethyl fumarate (DMF) and its primary metabolite monomethyl(More)
The extracellular matrix (ECM) provides signalling cues that regulate cell behaviour and orchestrate functions of cells in tissue formation and homeostasis. The composition of the ECM, its three-dimensional organization and proteolytic remodelling are major determinants of the microenvironmental signalling context that controls cell shape, motility, growth,(More)
RATIONALE In experimental models, lung fibrosis is dependent on transforming growth factor (TGF)-beta signaling. TGF-beta is secreted in a latent complex with its propeptide, and TGF-beta activators release TGF-beta from this complex. Because the integrin alpha(v)beta6 is a major TGF-beta activator in the lung, inhibition of alpha(v)beta6-mediated TGF-beta(More)
RATIONALE Transforming growth factor (TGF)-beta has a central role in driving many of the pathological processes that characterize pulmonary fibrosis. Inhibition of the integrin alpha(v)beta6, a key activator of TGF-beta in lung, is an attractive therapeutic strategy, as it may be possible to inhibit TGF-beta at sites of alpha(v)beta6 up-regulation without(More)
The transforming growth factor (TGF)-beta-inducible integrin alpha v beta6 is preferentially expressed at sites of epithelial remodeling and has been shown to bind and activate latent precursor TGF-beta. Herein, we show that alpha v beta6 is overexpressed in human kidney epithelium in membranous glomerulonephritis, diabetes mellitus, IgA nephropathy,(More)
The lymphotoxin-beta receptor (LT beta R) is a tumor necrosis factor receptor family member critical for the development and maintenance of various lymphoid microenvironments. Herein, we show that agonistic anti-LT beta R monoclonal antibody (mAb) CBE11 inhibited tumor growth in xenograft models and potentiated tumor responses to chemotherapeutic agents. In(More)
Components of lymphotoxin beta receptor (LTBR)-associated signaling complexes, including TRAF2, TRAF3, NIK, IKK1, and IKK2 have been shown to participate in the coupling of LTBR to NFkappaB. Here, we report that TRAF3 functions as a negative regulator of LTBR signaling via both canonical and non-canonical NFkappaB pathways by two distinct mechanisms.(More)
AIMS Gastro-resistant dimethyl fumarate (DMF) is an oral therapeutic indicated for the treatment of relapsing multiple sclerosis. Recent data suggest that a primary pharmacodynamic response to DMF treatment is activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway; however, the gene targets modulated downstream of NRF2 that contribute(More)