2024
Cellular Prion Protein Conformational Shift after Liquid–Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations
Liu Y, Tuttle M, Kostylev M, Roseman G, Zilm K, Strittmatter S. Cellular Prion Protein Conformational Shift after Liquid–Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations. Journal Of The American Chemical Society 2024, 146: 27903-27914. PMID: 39326869, PMCID: PMC11469297, DOI: 10.1021/jacs.4c10590.Peer-Reviewed Original ResearchConceptsLiquid-liquid phase separationCellular prion proteinAssociated with neurodegenerative diseasesAmyloid-bMaturation processDisordered proteinsPrion proteinConformational shiftProtein conformationConformational changesNeurodegenerative diseasesInduction conditionsConformational statesProteinPrPMutationsPhase separationSaturating concentrationsMolecular motionSolid-like stateMaturationDisease-related cognitive deficitsNeurodegenerationInductionAlzheimerLysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism
Takahashi H, Perez-Canamas A, Lee C, Ye H, Han X, Strittmatter S. Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism. Communications Biology 2024, 7: 1088. PMID: 39237682, PMCID: PMC11377756, DOI: 10.1038/s42003-024-06810-5.Peer-Reviewed Original ResearchConceptsMyelin lipid metabolismCo-immunoprecipitation assaysSulfated derivative sulfatideLipid metabolismAssociated with multiple neurological disordersCo-immunoprecipitationTMEM106BTransmembrane proteinsAmyloid fibrilsTMEM106B deficiencyHypomyelinating leukodystrophyAlzheimer's diseasePhysiological functionsFrontotemporal dementiaMolecular levelNeurodegenerative brainGalactosylceramidaseLipidomic analysisMultiple neurological disordersMetabolismMyelin lipidsDecreased levelsEndolysosomesAmyloidGalactosylceramidase activityWhole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease
Xicota L, Cosentino S, Vardarajan B, Mayeux R, Perls T, Andersen S, Zmuda J, Thyagarajan B, Yashin A, Wojczynski M, Krinsky‐McHale S, Handen B, Christian B, Head E, Mapstone M, Schupf N, Lee J, Barral S, Study T, Abner E, Adams P, Aguirre A, Albert M, Albin R, Allen M, Alvarez L, Andrews H, Apostolova L, Arnold S, Asthana S, Atwood C, Ayres G, Barber R, Barnes L, Barral S, Bartlett J, Beach T, Becker J, Beecham G, Benchek P, Bennett D, Bertelson J, Biber S, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Brewer J, Burke J, Burns J, Bush W, Buxbaum J, Byrd G, Cantwell L, Cao C, Carlsson C, Carrasquillo M, Chan K, Chasse S, Chen Y, Chesselet M, Chin N, Chui H, Chung J, Craft S, Crane P, Cranney M, Cruchaga C, Cuccaro M, Culhane J, Cullum C, Darby E, Davis B, De Jager P, DeCarli C, DeToledo J, Dickson D, Dobbins N, Duara R, Ertekin‐Taner N, Evans D, Faber K, Fairchild T, Fallin D, Fallon K, Fardo D, Farlow M, Farrell J, Farrer L, Fernandez‐Hernandez V, Foroud T, Frosch M, Galasko D, Gamboa A, Gauthreaux K, Gefen T, Geschwind D, Ghetti B, Gilbert J, Goate A, Grabowski T, Graff‐Radford N, Griswold A, Haines J, Hakonarson H, Hall K, Hall J, Hamilton R, Hamilton‐Nelson K, Han X, Harari O, Hardy J, Harrell L, Head E, Henderson V, Hernandez M, Honig L, Huebinger R, Huentelman M, Hulette C, Hyman B, Hynan L, Ibanez L, Jarvik G, Jayadev S, Jin L, Johnson K, Johnson L, Jones B, Jun G, Kamboh M, Kang M, Karydas A, Katz M, Kauwe J, Kaye J, Keene C, Keller B, Khaleeq A, Kim R, Knebl J, Kowall N, Kramer J, Kukull W, Kunkle B, Kuzma A, LaFerla F, Lah J, Larson E, Lerch M, Lerner A, Leung Y, Leverenz J, Levey A, Lieberman A, Lipton R, Lopez O, Lunetta K, Lyketsos C, Mains D, Manly J, Mark L, Marquez D, Marson D, Martin E, Masliah E, Massman P, Masurkar A, Mayeux R, McCormick W, McCurry S, McDonough S, McKee A, Mesulam M, Mez J, Miller B, Miller C, Mock C, Moghekar A, Montine T, Monuki E, Mooney S, Morris J, Mukherjee S, Myers A, Naj A, Nguyen T, Noble J, Nudelman K, O'Bryant S, Ormsby K, Ory M, Palmer R, Parisi J, Paulson H, Pavlik V, Paydarfar D, Perez V, Pericak‐Vance M, Petersen R, Polk M, Qu L, Quiceno M, Quinn J, Raj A, Rajabli F, Ramanan V, Reiman E, Reisch J, Reitz C, Ringman J, Roberson E, Rodriguear M, Rogaeva E, Rosen H, Rosenberg R, Royall D, Sano M, Saykin A, Schellenberg G, Schneider J, Schneider L, Seeley W, Sherva R, Shibata D, Small S, Smith A, Smith J, Song Y, Spina S, St George‐Hyslop P, Stern R, Stevens A, Strittmatter S, Sultzer D, Swerdlow R, Teich A, Tilson J, Tosto G, Trojanowski J, Troncoso J, Tsuang D, Valladares O, Van Deerlin V, Van Dyck C, Van Eldik L, Vance J, Vardarajan B, Vassar R, Vinters H, Wang L, Weintraub S, Welsh‐Bohmer K, Wheeler N, Wijsman E, Wilhelmsen K, Williams B, Williamson J, Wilms H, Wingo T, Wisniewski T, Woltjer R, Woon M, Younkin S, Yu L, Zhao Y, Zhou X, Zhu C, Aizenstein H, Ances B, Andrews H, Bell K, Birn R, Brickman A, Bulova P, Cheema A, Chen K, Christian B, Clare I, Cohen A, Constantino J, Doran E, Fagan A, Feingold E, Foroud T, Handen B, Harp J, Hartley S, Head E, Henson R, Hom C, Honig L, Ikonomovic M, Johnson S, Jordan C, Kamboh M, Keator D, Klunk W, Kofler J, Krinsky‐McHale S, Lai F, Lao P, Laymon C, Lee J, Lott I, Lupson V, Mapstone M, Mathis C, Minhas D, Nadkarni N, O'Bryant S, Parisi M, Pang D, Petersen M, Price J, Pulsifer M, Rafii M, Reiman E, Rizvi B, Rosas H, Ryan L, Schmitt F, Schupf N, Silverman W, Tudorascu D, Tumuluru R, Varadarajan B, White D, Yassa M, Zaman S, Zhang F. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 2670-2679. PMID: 38380866, PMCID: PMC11032545, DOI: 10.1002/alz.13718.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseGenes associated with late-onset Alzheimer's diseaseLate-onset Alzheimer's disease riskSeveral single nucleotide polymorphismsVariants associated with late-onset Alzheimer diseaseBeta-amyloidIdentified several single nucleotide polymorphismsWhole-genome sequence analysisGenome sequence analysisLevels of beta-amyloidAlzheimer's diseaseTight linkage disequilibriumMicrotubule associated proteinSingle nucleotide polymorphismsFamily studiesCandidate lociMTUS2Linkage disequilibriumSequence analysisAssociation analysisNucleotide polymorphismsGenetic associationAlzheimer's dementiaAssociated proteinGenetic componentReduced 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
2023
Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial
Howard E, Strittmatter S. Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial. Current Opinion In Neurology 2023, 36: 516-522. PMID: 37865850, PMCID: PMC10841037, DOI: 10.1097/wco.0000000000001205.Peer-Reviewed Original ResearchConceptsSpinal cord injuryChronic cervical spinal cord injuryCervical spinal cord injuryRecent clinical trialsCentral nervous systemClinical trialsAnimal studiesNeural repairChronic spinal cord injuryIncomplete spinal cord injuryTraumatic spinal cord injuryAdult mammalian central nervous systemContusion spinal cord injuryTreatment-naïve patientsSpinal cord traumaMammalian central nervous systemNeural repair therapiesUpper extremity strengthNonhuman primate studiesReceptor 1 pathwayNeurological recoveryNeurological deficitsCord traumaMedical therapyChronic stageAssociations of Sex, Race, and Apolipoprotein E Alleles With Multiple Domains of Cognition Among Older Adults
Walters S, Contreras A, Eissman J, Mukherjee S, Lee M, Choi S, Scollard P, Trittschuh E, Mez J, Bush W, Kunkle B, Naj A, Peterson A, Gifford K, Cuccaro M, Cruchaga C, Pericak-Vance M, Farrer L, Wang L, Haines J, Jefferson A, Kukull W, Keene C, Saykin A, Thompson P, Martin E, Bennett D, Barnes L, Schneider J, Crane P, Hohman T, Dumitrescu L, Abner E, Adams P, Aguirre A, Albert M, Albin R, Allen M, Alvarez L, Apostolova L, Arnold S, Asthana S, Atwood C, Ayres G, Barber R, Barnes L, Barral S, Bartlett J, Beach T, Becker J, Beecham G, Benchek P, Bennett D, Bertelson J, Biber S, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Brewer J, Burke J, Burns J, Bush W, Buxbaum J, Byrd G, Cantwell L, Cao C, Carlsson C, Carrasquillo M, Chan K, Chase S, Chen Y, Chesselet M, Chin N, Chui H, Chung J, Craft S, Crane P, Cruchaga C, Cuccaro M, Culhane J, Cullum C, Darby E, Davis B, DeCarli C, DeToledo J, Dickson D, Dobbins N, Duara R, Ertekin-Taner N, Evans D, Faber K, Fairchild T, Fallin D, Fallon K, Fardo D, Farlow M, Farrell J, Farrer L, Fernandez-Hernandez V, Foroud T, Frosch M, Galasko D, Gamboa A, Geschwind D, Ghetti B, Goate A, Grabowski T, Graff-Radford N, Griswold A, Haines J, Hakonarson H, Hall K, Hall J, Hamilton R, Hamilton-Nelson K, Han X, Hardy J, Harrell L, Head E, Henderson V, Hernandez M, Honig L, Huebinger R, Huentelman M, Hulette C, Hyman B, Hynan L, Ibanez L, De Jager P, Jarvik G, Jayadev S, Jin L, Johnson K, Johnson L, Jun G, Kamboh M, Kang M, Karydas A, Kathryn G, Katz M, Kauwe J, Kaye J, Keene C, Keller B, Khaleeq A, Kim R, Knebl J, Kowall N, Kramer J, Kukull W, Kunkle B, Kuzma A, LaFerla F, Lah J, Larson E, Lerch M, Lerner A, Leung Y, Leverenz J, Levey A, Li D, Lieberman A, Lipton R, Lopez O, Lunetta K, Lyketsos C, Mains D, Manly J, Mark L, Marquez D, Marson D, Martin E, Masliah E, Massman P, Masukar A, Mayeux R, McCormick W, McCurry S, McDonough S, McKee A, Mesulam M, Mez J, Miller B, Miller C, Mock C, Moghekar A, Montine T, Monuki E, Mooney S, Morris J, Mukherjee S, Myers A, Naj A, Nguyen T, O'Bryant S, Ormsby K, Ory M, Palmer R, Parisi J, Paulson H, Pavlik V, Paydarfar D, Perez V, Pericak-Vance M, Peterson R, Polk M, Qu L, Quiceno M, Quinn J, Raj A, Rajabli F, Ramanan V, Reiman E, Reisch J, Reitz C, Ringman J, Robertson E, Rodriguear M, Rogaeva E, Rosen H, Rosenberg R, Royall D, Sano M, Saykin A, Schellenberg G, Schneider J, Schneider L, Seeley W, Sherva R, Shibata D, Small S, Smith A, Smith J, Song Y, Spina S, St George-Hyslop P, Stern R, Stevens A, Strittmatter S, Sultzer D, Swerdlow R, Tilson J, Tosto G, Trojanowski J, Troncoso J, Tsuang D, Valladares O, Vance J, Van Deerlin V, Van Eldik L, Vardarajan B, Vassar R, Vinters H, Vonsattel J, Wang L, Weintraub S, Welsh-Bohmer K, Wheeler N, Wijsman E, Wilhelmsen K, Williams S, Williams B, Williamson J, Wilms H, Wingo T, Woltjer R, Woon M, Younkin S, Yu L, Zhao Y, Zhou X, Zhu C, Adegoke O, Aisen P, Apostolova L, Ashford M, Beckett L, Bernard M, Bernhardt H, Borowski B, Cabrera Y, Cairns N, Carrillo M, Chen K, Choe M, Clanton T, Coker G, Conti C, Crawford K, Das S, Donohue M, Fleisher A, Flenneiken D, Fletcher E, Fockler J, Forghanian-Arani A, Foroud T, Fox N, Franklin E, Gessert D, González H, Green R, Gunter J, Harvey D, Hergesheimer L, Ho C, Householder E, Hsaio J, Jack C, Jackson J, Jagust W, Jahanshad N, Jimenez G, Jin C, Jones D, Kantarci K, Khachaturian Z, Knaack A, Koeppe R, Kormos A, Landau S, Mahboubi P, Malone I, Masterman D, Mathis C, Miller G, Montine T, Moore S, Morris J, Neu S, Neuhaus J, Nho K, Nir T, Nosheny R, Nudelman K, Okonkwo O, Perrin R, Pizzola J, Potter W, Rafii M, Raman R, Reid R, Reiman E, Risacher S, Rossi Chen S, Ryan L, Salazar J, Saykin A, Schwarz C, Senjem M, Shaffer E, Shaw L, Shen L, Silverberg N, Smith S, Taylor-Reinwald L, Thal L, Thomopoulos S, Thompson P, Toga A, Tosun-Turgut D, Trojanowski J, Truran Sacrey D, Veitch D, Vemuri P, Walter S, Ward C, Weiner M, Wilmes K, Yushkevich P, Zimmerman C. Associations of Sex, Race, and Apolipoprotein E Alleles With Multiple Domains of Cognition Among Older Adults. JAMA Neurology 2023, 80: 929-939. PMID: 37459083, PMCID: PMC10352930, DOI: 10.1001/jamaneurol.2023.2169.Peer-Reviewed Original ResearchSoluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial
Maynard G, Kannan R, Liu J, Wang W, Lam T, Wang X, Adamson C, Hackett C, Schwab J, Liu C, Leslie D, Chen D, Marino R, Zafonte R, Flanders A, Block G, Smith E, Strittmatter S. Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial. The Lancet Neurology 2023, 22: 672-684. PMID: 37479373, PMCID: PMC10410101, DOI: 10.1016/s1474-4422(23)00215-6.Peer-Reviewed Original ResearchConceptsUpper extremity motor scoreSpinal cord injuryChronic spinal cord injuryTreatment-related adverse eventsAdverse eventsDay 169Intrathecal dosesCord injuryClinical trialsAmerican Spinal Injury Association Impairment Scale (AIS) gradeCervical traumatic spinal cord injuryChronic cervical spinal cord injuryCommon treatment-related adverse eventsCervical spinal cord injurySevere spinal cord injuryTraumatic spinal cord injuryPost-hoc subgroup analysesPersistent neurological deficitsDouble-blind comparisonKey secondary objectiveNational InstituteOpen labelAdvancing Translational SciencesPlacebo groupNeurological deficits
2022
Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2
Rodriguez CM, Bechek SC, Jones GL, Nakayama L, Akiyama T, Kim G, Solow-Cordero DE, Strittmatter SM, Gitler AD. Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2. Cell Reports 2022, 41: 111505. PMID: 36288715, PMCID: PMC9664481, DOI: 10.1016/j.celrep.2022.111505.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisSpinocerebellar ataxia type 2Nogo receptorAtaxin-2 levelsNovel therapeutic targetNeurodegenerative disease amyotrophic lateral sclerosisGene-based therapeutic strategiesDisease amyotrophic lateral sclerosisNerve injuryAtaxin-2Axonal regenerationAxonal regrowthLateral sclerosisTherapeutic strategiesHuman neuronsKnockout miceTherapeutic targetPotential treatmentType 2Protein levelsPotent modifierProtein ataxin-2Additional strategiesMiceRNA screenMolecular and cellular evolution of the primate dorsolateral prefrontal cortex
Ma S, Skarica M, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R, Krsnik Ž, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman-Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin MR, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM, Sousa AMM, Sestan N. Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science 2022, 377: eabo7257. PMID: 36007006, PMCID: PMC9614553, DOI: 10.1126/science.abo7257.Peer-Reviewed Original ResearchConceptsMolecular differencesSingle-nucleus transcriptomesSubset of speciesNeuropsychiatric risk genesCellular evolutionCellular repertoireEvolutionary specializationDorsolateral prefrontal cortexRate-limiting enzymeDivergent featuresRisk genesAnthropoid primatesPrefrontal cortexPrimate dorsolateral prefrontal cortexCertain interneuronsNeuropeptide somatostatinDopamine productionGranular neuronsTyrosine hydroxylaseCell subtypesExpressionTranscriptomeAdult humansGenesPrimatesIFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses
Clement M, Forbester J, Marsden M, Sabberwal P, Sommerville M, Wellington D, Dimonte S, Clare S, Harcourt K, Yin Z, Nobre L, Antrobus R, Jin B, Chen M, Makvandi-Nejad S, Lindborg J, Strittmatter S, Weekes M, Stanton R, Dong T, Humphreys I. IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses. Nature Communications 2022, 13: 5294. PMID: 36075894, PMCID: PMC9454482, DOI: 10.1038/s41467-022-32587-4.Peer-Reviewed Original ResearchConceptsInterferon-induced transmembrane protein 3IL-6 productionViral pathogenesisCytokine productionPro-inflammatory cytokine productionInflammatory cytokine productionInflammatory cytokine responseSARS-CoV-2Transmembrane protein 3Dendritic cellsCytokine responsesImmunoregulatory pathwaysImmunoregulatory functionsTLR2 responsesTLR responsesMouse modelMyeloid cellsViral stimulationProtein 3PathogenesisRestriction factorsNogoCellular localizationResponseCellsAlzheimer 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 functionTranslational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM
Fang H, Rossano S, Wang X, Nabulsi N, Kelley B, Fowles K, Ropchan J, Strittmatter SM, Carson RE, Huang Y. Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM. Molecular Imaging And Biology 2022, 24: 560-569. PMID: 35020138, PMCID: PMC9550197, DOI: 10.1007/s11307-021-01698-7.Peer-Reviewed Original ResearchConceptsSpinal cord injurySpinal cordHealthy ratsHuman spinal cordCord injurySerotonin transporterRat modelRodent modelsPET imagingTranslational PET imagingSCI rat modelIntact spinal cordSpinal cord caudalRodent spinal cordSerotonin transporter tracerUse of PETCervical uptakeSERT changesSCI animalsSCI patientsPresynaptic serotonin transporterCord caudalAxon damageSerotonin systemSERT radioligand
2021
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells
Franjic D, Skarica M, Ma S, Arellano JI, Tebbenkamp ATN, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Zhang S, Liu Y, Spurrier J, Zhang L, Gudelj I, Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 2021, 110: 452-469.e14. PMID: 34798047, PMCID: PMC8813897, DOI: 10.1016/j.neuron.2021.10.036.Peer-Reviewed Original ResearchConceptsDisease-related proteinsCellular diversityCross-species analysisSingle-nucleus transcriptomesLipid droplet proteinsSpecies-specific propertiesImmature neuron populationTranscriptomic taxonomyAlzheimer's disease-related proteinsEndoplasmic reticulumCell typesHuman neuronsSpecies differencesHistologic signatureNeurogenic capabilityProteinExcitatory neuronsDiversityAdult miceGranule cellsAlzheimer's diseaseNeuron populationsCognitive functionEntorhinal cellsAdult humansOptic nerve regeneration screen identifies multiple genes restricting adult neural repair
Lindborg JA, Tran NM, Chenette DM, DeLuca K, Foli Y, Kannan R, Sekine Y, Wang X, Wollan M, Kim IJ, Sanes JR, Strittmatter SM. Optic nerve regeneration screen identifies multiple genes restricting adult neural repair. Cell Reports 2021, 34: 108777. PMID: 33657370, PMCID: PMC8009559, DOI: 10.1016/j.celrep.2021.108777.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCRISPR-Cas SystemsDependovirusFemaleGene EditingGene Expression RegulationGenetic Association StudiesHEK293 CellsHumansInterleukinsMaleMAP Kinase Kinase KinasesMice, Inbred C57BLMice, TransgenicNerve RegenerationNeurogenesisOptic NerveOptic Nerve InjuriesRetinal Ganglion CellsSignal TransductionSTAT3 Transcription FactorConceptsOptic nerve crushRetinal ganglion cellsRegeneration-associated genesShort hairpin RNAIL-22Neural repairCentral nervous system traumaNeurological deficits persistNervous system traumaNerve crushAxonal damageAxonal regenerationGanglion cellsSystem traumaInflammatory responseCNS regenerationDeficits persistAxonal growthHairpin RNAConcurrent activationTranscription 3Cell-autonomous factorsKinase pathwaySignal transducerRepairB-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
Bakhuraysah MM, Theotokis P, Lee JY, Alrehaili AA, Aui PM, Figgett WA, Azari MF, Abou-Afech JP, Mackay F, Siatskas C, Alderuccio F, Strittmatter SM, Grigoriadis N, Petratos S. B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF. Scientific Reports 2021, 11: 2890. PMID: 33536561, PMCID: PMC7858582, DOI: 10.1038/s41598-021-82346-6.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisEAE-induced miceB cellsB-cell activating factorMeningeal B cellsLumbosacral spinal cordSecretion of immunoglobulinsG0/G1 phaseImmune cell signalingNeurological progressionAutoimmune encephalomyelitisInflammatory infiltrateAxonal dystrophyCentral nervous system myelinSpinal cordRecombinant BAFFActivating factorNgR1Score 1BAFFBAFF stimulationInfiltratesNgR3System myelinG1 phaseNovel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel
Kunkle BW, Schmidt M, Klein HU, Naj AC, Hamilton-Nelson KL, Larson EB, Evans DA, De Jager PL, Crane PK, Buxbaum JD, Ertekin-Taner N, Barnes LL, Fallin MD, Manly JJ, Go RCP, Obisesan TO, Kamboh MI, Bennett DA, Hall KS, Goate AM, Foroud TM, Martin ER, Wang L, Byrd GS, Farrer LA, Haines JL, Schellenberg GD, Mayeux R, Pericak-Vance MA, Reitz C, Abner E, Adams P, Albin R, Apostolova L, Arnold S, Atwood C, Baldwin C, Barber R, Barral S, Beach T, Becker J, Beecham G, Bigio E, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Burke J, Burns J, Cairns N, Cao C, Carlsson C, Carney R, Carrasquillo M, Cribbs D, Cruchaga C, Dick M, Dickson D, Doody R, Duara R, Faber K, Fairchild T, Fallon K, Fardo D, Farlow M, Ferris S, Frosch M, Galasko D, Gearing M, Geschwind D, Ghetti B, Gilbert J, Green R, Growdon J, Hakonarson H, Hamilton R, Hardy J, Harrell L, Honig L, Huebinger R, Huentelman M, Hulette C, Jarvik G, Jin L, Karydas A, Katz M, Kauwe J, Keene C, Kim R, Kramer J, Lah J, Leung Y, Li G, Lieberman A, Lipton R, Lyketsos C, Malamon J, Marson D, Martiniuk F, Masliah E, McCormick W, McCurry S, McDavid A, McDonough S, McKee A, Mesulam M, Miller B, Miller C, Montine T, Mukherjee S, Myers A, O’Bryant S, Olichney J, Parisi J, Peskind E, Pierce A, Poon W, Potter H, Qu L, Quinn J, Raj A, Raskind M, Reisberg B, Reisch J, Ringman J, Roberson E, Rogaeva E, Rosen H, Royall D, Sager M, Schneider J, Schneider L, Seeley W, Small S, Sonnen J, Spina S, St George-Hyslop P, Stern R, Tanzi R, Troncoso J, Tsuang D, Valladares O, Van Deerlin V, Vardarajan B, Vinters H, Vonsattel J, Weintraub S, Welsh-Bohmer K, Wilhelmsen K, Williamson J, Wingo T, Woltjer R, Wu C, Younkin S, Yu L, Yu C, Zhao Y, Graff-Radford N, Martinez I, Ayodele T, Logue M, Cantwell L, Jean-Francois M, Kuzma A, Adams L, Vance J, Cuccaro M, Chung J, Mez J, Lunetta K, Jun G, Lopez O, Hendrie H, Reiman E, Kowall N, Leverenz J, Small S, Levey A, Golde T, Saykin A, Starks T, Albert M, Hyman B, Petersen R, Sano M, Wisniewski T, Vassar R, Kaye J, Henderson V, DeCarli C, LaFerla F, Brewer J, Miller B, Swerdlow R, Van Eldik L, Paulson H, Trojanowski J, Chui H, Rosenberg R, Craft S, Grabowski T, Asthana S, Morris J, Strittmatter S, Kukull W. Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel. JAMA Neurology 2021, 78: 102-113. PMID: 33074286, PMCID: PMC7573798, DOI: 10.1001/jamaneurol.2020.3536.Peer-Reviewed Original ResearchConceptsIntergenic lociRisk lociAlzheimer's disease genome-wide association studiesGenome-wide association studiesGenome-wide associationDisease-associated lociAlzheimer's Disease Genetics ConsortiumDisease risk lociLargest association analysisAdditional risk lociAlzheimer’s disease risk lociGene expression dataTrafficking pathwaysAdditional lociPathway analysisAssociation studiesExpression dataAssociation analysisSuggestive significanceLociFamily-based data setCommon locusNovel mechanismAlzheimer's disease etiologyGenetics Consortium
2020
Gene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in
Chiasseu M, Fesharaki-Zadeh A, Saito T, Saido TC, Strittmatter SM. Gene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in. Neurobiology Of Disease 2020, 145: 105059. PMID: 32858147, PMCID: PMC7572902, DOI: 10.1016/j.nbd.2020.105059.Peer-Reviewed Original ResearchConceptsMild traumatic brain injuryTraumatic brain injuryAlzheimer's diseaseBrain injuryGene-environment interactionsMild closed head injuryMorris water maze testAge-matched wild-type controlsStrong unmet needAccumulation of amyloidAge-matched miceClosed head injuryWater maze testNovel object recognitionPersistent cognitive deficitsProtein gene mutationsIba1 expressionWild-type controlsPhospho-tauClinical manifestationsAD pathologyAD symptomsHead injuryAD pathogenesisRisk factorsFyn 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 learningThe stress-responsive gene GDPGP1/mcp-1 regulates neuronal glycogen metabolism and survival
Schulz A, Sekine Y, Oyeyemi MJ, Abrams AJ, Basavaraju M, Han SM, Groth M, Morrison H, Strittmatter SM, Hammarlund M. The stress-responsive gene GDPGP1/mcp-1 regulates neuronal glycogen metabolism and survival. Journal Of Cell Biology 2020, 219: e201807127. PMID: 31968056, PMCID: PMC7041677, DOI: 10.1083/jcb.201807127.Peer-Reviewed Original ResearchConceptsNeuronal stress resistanceStress resistanceNovel cellular responsesMouse neuronsVariety of stressesCaenorhabditis elegansC. elegansTranscriptional analysisSingle homologueEnvironmental stressFunctional characterizationCellular responsesCell deathNeuronal cell deathNeuronal glycogenGlycogen metabolismWidespread neuronal cell deathElegansSurvival of animalsTauopathy modelMaladaptive responsesKey roleHomologuesGlycogen levelsKnockdownPET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex