2025
Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice
Lin J, Callender J, Mayfield J, McClatchy D, Ojeda-Juárez D, Pourhamzeh M, Soldau K, Kurt T, Danque G, Khuu H, Ronson J, Pizzo D, Du Y, Gruber M, Sevillano A, Wang J, Orrú C, Chen J, Funk G, Aguilar-Calvo P, Aulston B, Roy S, Rho J, Bui J, Newton A, Lipton S, Caughey B, Patrick G, Doré K, Yates J, Sigurdson C. Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice. Journal Of Clinical Investigation 2025, 135: e186432. PMID: 40185484, PMCID: PMC12077891, DOI: 10.1172/jci186432.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsProtein kinase CAmino terminusPrion proteinN-methyl-D-aspartateMutant prion proteinNMDA receptor activationN-linked glycosylation sitesExcitatory-inhibitory imbalanceHippocampal pyramidal neuronsDownstream signaling eventsActivate protein kinase CNMDAR channelsNeuronal hyperexcitabilityFunctional motifsGlutamate receptorsCalcium influxPhosphoproteomic analysisPyramidal neuronsGlycosylation sitesSignaling eventsReceptor activationPrion-infected miceDendritic beadingSynapse loss
2013
Activation of AMPK Enhances Neutrophil Chemotaxis and Bacterial Killing
Park D, Jiang S, Tadie J, Stigler W, Gao Y, Deshane J, Abraham E, Zmijewski J. Activation of AMPK Enhances Neutrophil Chemotaxis and Bacterial Killing. Molecular Medicine 2013, 19: 387-398. PMID: 24091934, PMCID: PMC3883969, DOI: 10.2119/molmed.2013.00065.Peer-Reviewed Original ResearchMeSH KeywordsActinsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsBacteremiaChemotaxis, LeukocyteEnzyme ActivationHeterocyclic Compounds, 3-RingHL-60 CellsHumansMaleMetforminMiceMice, Inbred C57BLNeutrophilsPeritonitisPhagocytosisPhosphorylationProtein Kinase InhibitorsPyridinesRibonucleotidesRNA, Small InterferingSignal TransductionSirolimusConceptsAdenosine monophosphate-activated protein kinaseAminoimidazole carboxamide ribonucleotideActivation of adenosine monophosphate-activated protein kinaseTreatment of neutrophilsAdenosine monophosphate-activated protein kinase activationBacterial killingSmall interfering RNA (siRNA)-mediated knockdownBlockade of AMPK activationAdenosine monophosphate-activated protein kinase inhibitor Compound CIkBa degradationMonophosphate-activated protein kinaseInhibitor compound CDownstream signaling eventsLPS/Toll-like receptor 4Inhibition of chemotaxisActin polymerizationAMPK activationAMPK phosphorylationCompound CSignaling eventsProtein kinaseInability of neutrophilsNeutrophil motilityAssociated with severe infectionsInvading microorganisms
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