2020
Fronto-temporal dementia risk gene TMEM106B has opposing effects in different lysosomal storage disorders
Perez-Canamas A, Takahashi H, Lindborg JA, Strittmatter SM. Fronto-temporal dementia risk gene TMEM106B has opposing effects in different lysosomal storage disorders. Brain Communications 2020, 3: fcaa200. PMID: 33796852, PMCID: PMC7990118, DOI: 10.1093/braincomms/fcaa200.Peer-Reviewed Original ResearchNeuronal ceroid lipofuscinosisLysosomal compartmentGenome-wide association studiesCeroid lipofuscinosisGaucher diseaseLysosomal storage disorderEndo-lysosomal compartmentsTransmembrane proteinStorage disorderVacuolar ATPaseNull phenotypeATPase stateFrontotemporal lobar degenerationAssociation studiesConduritol B epoxidePurkinje cell degenerationLysosomal acidificationMouse phenotypeNeurodegenerative lysosomal diseaseDifferent lysosomal storage disordersTMEM106BNeuronal lossMotor deficitsNeuronal degenerationPhenotype
2017
Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice
Klein ZA, Takahashi H, Ma M, Stagi M, Zhou M, Lam TT, Strittmatter SM. Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice. Neuron 2017, 95: 281-296.e6. PMID: 28728022, PMCID: PMC5558861, DOI: 10.1016/j.neuron.2017.06.026.Peer-Reviewed Original ResearchConceptsLysosomal protein levelsFrontotemporal lobar degenerationProtein levelsMultiple lysosomal enzymesLysosomal enzymesV0 subunitsTMEM106B geneProteomic analysisProgranulin-deficient miceExtent of neurodegenerationCommon neurodegenerative disorderLysosomal acidificationLysosomal enzyme levelsProtein 1Microglial accumulationRisk modificationFTLD riskBehavioral abnormalitiesRetinal degenerationNeurodegenerative disordersFrontotemporal dementiaGRNTMEM106BFunctional relationshipEnzyme levelsOpposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network
Takahashi H, Klein ZA, Bhagat SM, Kaufman AC, Kostylev MA, Ikezu T, Strittmatter SM, For the Alzheimer’s Disease Neuroimaging Initiative. Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta Neuropathologica 2017, 133: 785-807. PMID: 28070672, PMCID: PMC5391267, DOI: 10.1007/s00401-017-1668-z.Peer-Reviewed Original ResearchConceptsAPP/PS1 micePS1 micePGRN deficiencyAlzheimer's diseaseAD risk variantsCerebrospinal fluid Aβ levelsLoss of progranulinMicroglial Aβ phagocytosisCSF tau levelsFrontotemporal lobar degenerationRisk variantsAPPswe/Aβ phagocytosisNeuronal injuryAβ levelsAβ pathologyCerebral amyloidosisAxonal dystrophyTau pathologyTau levelsComplement depositionPGRN levelsAD pathophysiologyAmyloid imagingProgranulin deficiency
2012
Vps10 Family Proteins and the Retromer Complex in Aging-Related Neurodegeneration and Diabetes
Lane RF, St George-Hyslop P, Hempstead BL, Small SA, Strittmatter SM, Gandy S. Vps10 Family Proteins and the Retromer Complex in Aging-Related Neurodegeneration and Diabetes. Journal Of Neuroscience 2012, 32: 14080-14086. PMID: 23055476, PMCID: PMC3576841, DOI: 10.1523/jneurosci.3359-12.2012.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorType 2 diabetes mellitusNeurotrophic signaling pathwaysFrontotemporal lobar degenerationNon-neuronal cellsPathogenesis of neurodegenerationGenetic risk factorsBDNF levelsDiabetes mellitusFamily of receptorsNeurotrophic factorRisk factorsParkinson's diseaseTrk receptorsAcute responseAutosomal dominant formAlzheimer's diseaseNeurodegenerative diseasesDiseaseCell surface receptorsReceptorsSignaling pathwaysSurface receptorsPleiotropic functionsIntracellular responses
2010
Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin
Hu F, Padukkavidana T, Vægter CB, Brady OA, Zheng Y, Mackenzie IR, Feldman HH, Nykjaer A, Strittmatter SM. Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin. Neuron 2010, 68: 654-667. PMID: 21092856, PMCID: PMC2990962, DOI: 10.1016/j.neuron.2010.09.034.Peer-Reviewed Original ResearchConceptsFrontotemporal lobar degenerationSerum PGRN levelsFTLD-TDP casesFTLD-TDPMicroglial cellsPGRN levelsCortical neuronsGRN haploinsufficiencyProgranulin mutationsTDP-43Causative rolePGRNUbiquitin aggregatesNeuronsSortilinMiceCell surfaceDetermine levelsPathophysiologyInjuryProgranulinCNSCentral roleDegenerationBrain