FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2107514209> ?p ?o ?g. }

• W2107514209 endingPage "14740" @default.
• W2107514209 startingPage "14735" @default.
• W2107514209 abstract "Disruption of the blood–brain barrier (BBB) is a hallmark of acute inflammatory lesions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis. This disruption may precede and facilitate the infiltration of encephalitogenic T cells. The signaling events that lead to this BBB disruption are incompletely understood but appear to involve dysregulation of tight-junction proteins such as claudins. Pharmacological interventions aiming at stabilizing the BBB in MS might have therapeutic potential. Here, we show that the orally available small molecule LY-317615, a synthetic bisindolylmaleimide and inhibitor of protein kinase Cβ, which is clinically under investigation for the treatment of cancer, suppresses the transmigration of activated T cells through an inflamed endothelial cell barrier, where it leads to the induction of the tight-junction molecules zona occludens-1, claudin 3, and claudin 5 and other pathways critically involved in transendothelial leukocyte migration. Treatment of mice with ongoing experimental autoimmune encephalomyelitis with LY-317615 ameliorates inflammation, demyelination, axonal damage, and clinical symptoms. Although LY-317615 dose-dependently suppresses T-cell proliferation and cytokine production independent of antigen specificity, its therapeutic effect is abrogated in a mouse model requiring pertussis toxin. This abrogation indicates that the anti-inflammatory and clinical efficacy is mainly mediated by stabilization of the BBB, thus suppressing the transmigration of encephalitogenic T cells. Collectively, our data suggest the involvement of endothelial protein kinase Cβ in stabilizing the BBB in autoimmune neuroinflammation and imply a therapeutic potential of BBB-targeting agents such as LY-317615 as therapeutic approaches for MS." @default.
• W2107514209 created "2016-06-24" @default.
• W2107514209 creator A5005418771 @default.
• W2107514209 creator A5011103119 @default.
• W2107514209 creator A5011846421 @default.
• W2107514209 creator A5017640916 @default.
• W2107514209 creator A5018419730 @default.
• W2107514209 creator A5019908745 @default.
• W2107514209 creator A5034872348 @default.
• W2107514209 creator A5039985608 @default.
• W2107514209 creator A5040381414 @default.
• W2107514209 creator A5042378326 @default.
• W2107514209 creator A5043741628 @default.
• W2107514209 creator A5045013615 @default.
• W2107514209 creator A5052657395 @default.
• W2107514209 creator A5057857185 @default.
• W2107514209 creator A5059575429 @default.
• W2107514209 creator A5063978061 @default.
• W2107514209 creator A5064778456 @default.
• W2107514209 creator A5080482957 @default.
• W2107514209 creator A5082334179 @default.
• W2107514209 date "2013-08-19" @default.
• W2107514209 modified "2023-10-18" @default.
• W2107514209 title "Protein kinase Cβ as a therapeutic target stabilizing blood–brain barrier disruption in experimental autoimmune encephalomyelitis" @default.
• W2107514209 cites W1530073982 @default.
• W2107514209 cites W1555886595 @default.
• W2107514209 cites W1638810975 @default.
• W2107514209 cites W1796054280 @default.
• W2107514209 cites W1968814315 @default.
• W2107514209 cites W1973763077 @default.
• W2107514209 cites W1980661152 @default.
• W2107514209 cites W1985775190 @default.
• W2107514209 cites W1988384513 @default.
• W2107514209 cites W1992017089 @default.
• W2107514209 cites W1999959667 @default.
• W2107514209 cites W2001267675 @default.
• W2107514209 cites W2001616488 @default.
• W2107514209 cites W2009313724 @default.
• W2107514209 cites W2011914090 @default.
• W2107514209 cites W2013152182 @default.
• W2107514209 cites W2013517841 @default.
• W2107514209 cites W2015210347 @default.
• W2107514209 cites W2021362957 @default.
• W2107514209 cites W2024530909 @default.
• W2107514209 cites W2025658823 @default.
• W2107514209 cites W2029638304 @default.
• W2107514209 cites W2031880075 @default.
• W2107514209 cites W2033859994 @default.
• W2107514209 cites W2042673910 @default.
• W2107514209 cites W2044400894 @default.
• W2107514209 cites W2045454822 @default.
• W2107514209 cites W2053318593 @default.
• W2107514209 cites W2058852699 @default.
• W2107514209 cites W2060844162 @default.
• W2107514209 cites W2064623974 @default.
• W2107514209 cites W2068105241 @default.
• W2107514209 cites W2068553109 @default.
• W2107514209 cites W2068609129 @default.
• W2107514209 cites W2071205488 @default.
• W2107514209 cites W2091805482 @default.
• W2107514209 cites W2094631886 @default.
• W2107514209 cites W2097573610 @default.
• W2107514209 cites W2107422246 @default.
• W2107514209 cites W2120601121 @default.
• W2107514209 cites W2123808042 @default.
• W2107514209 cites W2126372596 @default.
• W2107514209 cites W2130284499 @default.
• W2107514209 cites W2140881278 @default.
• W2107514209 cites W2144442541 @default.
• W2107514209 cites W2156635509 @default.
• W2107514209 cites W2159334049 @default.
• W2107514209 cites W2159888487 @default.
• W2107514209 cites W2163830368 @default.
• W2107514209 cites W2167279371 @default.
• W2107514209 cites W2167947851 @default.
• W2107514209 cites W2172187886 @default.
• W2107514209 cites W4243450814 @default.
• W2107514209 doi "https://doi.org/10.1073/pnas.1302569110" @default.
• W2107514209 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3767524" @default.
• W2107514209 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23959874" @default.
• W2107514209 hasPublicationYear "2013" @default.
• W2107514209 type Work @default.
• W2107514209 sameAs 2107514209 @default.
• W2107514209 citedByCount "42" @default.
• W2107514209 countsByYear W21075142092013 @default.
• W2107514209 countsByYear W21075142092014 @default.
• W2107514209 countsByYear W21075142092015 @default.
• W2107514209 countsByYear W21075142092016 @default.
• W2107514209 countsByYear W21075142092017 @default.
• W2107514209 countsByYear W21075142092018 @default.
• W2107514209 countsByYear W21075142092019 @default.
• W2107514209 countsByYear W21075142092020 @default.
• W2107514209 countsByYear W21075142092021 @default.
• W2107514209 countsByYear W21075142092022 @default.
• W2107514209 crossrefType "journal-article" @default.
• W2107514209 hasAuthorship W2107514209A5005418771 @default.
• W2107514209 hasAuthorship W2107514209A5011103119 @default.
• W2107514209 hasAuthorship W2107514209A5011846421 @default.

• next