2024
Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase
Takahashi H, Bhagwagar S, Nies S, Ye H, Han X, Chiasseu M, Wang G, Mackenzie I, Strittmatter S. Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase. Nature Communications 2024, 15: 1434. PMID: 38365772, PMCID: PMC10873339, DOI: 10.1038/s41467-024-45692-3.Peer-Reviewed Original ResearchConceptsTau inclusionsComorbid proteinopathiesTau aggregation in vitroPromotes tau aggregation in vitroAlzheimer's diseaseProgranulin reductionTDP-43 proteinopathyTauopathy phenotypeTau aggregationAD-tauHuman tauopathiesNeurofibrillary tanglesTauopathy miceReduction of progranulinPurified GlcCerTDP-43Concomitant accumulationAggregation in vitroAssociated with synucleinopathiesNeurodegenerative disordersProteinopathiesGCase inhibitionTauGCaseGlcCer
2022
Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy
Brody AH, Nies SH, Guan F, Smith LM, Mukherjee B, Salazar SA, Lee S, Lam TKT, Strittmatter SM. Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy. Molecular Neurodegeneration 2022, 17: 32. PMID: 35501917, PMCID: PMC9063299, DOI: 10.1186/s13024-022-00526-y.Peer-Reviewed Original ResearchConceptsPS19 miceTau phosphorylationDisease riskPyk2 expressionPyk2 activityHuman neuronal culturesAlzheimer's disease riskNeuro-inflammationSynapse lossTau accumulationTau pathologyMouse survivalC1q depositionT cellsAssociated pathologyMouse modelLittermate controlsMAPK activityHuman neuronsHuman tauNeuronal culturesPyk2 inhibitionVivo modelMouse brainSynaptic function
2020
Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy
Tang SJ, Fesharaki-Zadeh A, Takahashi H, Nies SH, Smith LM, Luo A, Chyung A, Chiasseu M, Strittmatter SM. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathologica Communications 2020, 8: 96. PMID: 32611392, PMCID: PMC7329553, DOI: 10.1186/s40478-020-00976-9.Peer-Reviewed Original ResearchConceptsRepetitive closed head injuriesMemory deficitsPhospho-tau accumulationChronic variable stressPersistent memory deficitsP301S transgenic miceClosed head injuryFyn inhibitionPassive avoidance learningFyn kinaseGlial activationPhospho-tauPresynaptic markersSynapse lossTau accumulationHead injurySynapse densityPhosphorylated tauTherapeutic benefitTransgenic miceBehavioral improvementTrauma modelTauopathiesSpatial memoryAvoidance learning