2022
Inhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke
Bitar L, Uphaus T, Thalman C, Muthuraman M, Gyr L, Ji H, Domingues M, Endle H, Groppa S, Steffen F, Koirala N, Fan W, Ibanez L, Heitsch L, Cruchaga C, Lee JM, Kloss F, Bittner S, Nitsch R, Zipp F, Vogt J. Inhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke. Science Translational Medicine 2022, 14: eabk0135. PMID: 35442704, DOI: 10.1126/scitranslmed.abk0135.Peer-Reviewed Original ResearchConceptsStroke outcomeExperimental strokeGlutamatergic transmissionCortical excitabilityATX concentrationsAstrocyte-specific deletionDifferent time pointsStroke eventsPerisynaptic processesExcess glutamateTherapeutic approachesAnimal modelsTransgenic miceEnzyme autotaxinLPA signalingATX inhibitionPharmacological inhibitionStrokeTranslational potentialTime pointsSingle nucleotide polymorphismsAutotaxinOutcomesExcitabilityInhibition
2011
Kinetic Analysis of Autotaxin Reveals Substrate-specific Catalytic Pathways and a Mechanism for Lysophosphatidic Acid Distribution*
Saunders LP, Cao W, Chang WC, Albright RA, Braddock DT, De La Cruz EM. Kinetic Analysis of Autotaxin Reveals Substrate-specific Catalytic Pathways and a Mechanism for Lysophosphatidic Acid Distribution*. Journal Of Biological Chemistry 2011, 286: 30130-30141. PMID: 21719699, PMCID: PMC3191052, DOI: 10.1074/jbc.m111.246884.Peer-Reviewed Original ResearchConceptsLysophosphatidic acidSecreted lysophospholipase DThr-210Synthase cycleVivo substrateSubstrate bindingQuantitative physiological modelsSignaling cascadesPosition 210LPA signalingCatalytic threonineFluorescent lipidLysophospholipase DCancer metastasisSlow catalysisCatalytic pathwayDiazol-4PathwayAutotaxinProduct releaseBindsLPA synthesisFS-3Acid distributionBioactive form
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