2023
Amino-terminal proteolytic fragment of the axon growth inhibitor Nogo-A (Rtn4A) is upregulated by injury and promotes axon regeneration
Sekine Y, Wang X, Kikkawa K, Honda S, Strittmatter S. Amino-terminal proteolytic fragment of the axon growth inhibitor Nogo-A (Rtn4A) is upregulated by injury and promotes axon regeneration. Journal Of Biological Chemistry 2023, 299: 105232. PMID: 37690690, PMCID: PMC10622843, DOI: 10.1016/j.jbc.2023.105232.Peer-Reviewed Original ResearchConceptsAxon regenerationCentral nervous system injuryPersistent neurological deficitsCerebral cortical neuronsNervous system injuryNeurological deficitsSystem injuryCNS injuryCortical neuronsAmino-terminal fragmentInjuryExtracellular actionPhysiological productionNogoInhibitory proteinMiceNeuronsInhibitory domainOverexpression increasesVaried resultsProteolytic fragmentsAxotomyExpressionNogoAGene targetingAssociations 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
2021
NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates
Boghdadi AG, Spurrier J, Teo L, Li M, Skarica M, Cao B, Kwan WC, Merson TD, Nilsson SK, Sestan N, Strittmatter SM, Bourne JA. NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates. Nature Communications 2021, 12: 6906. PMID: 34824275, PMCID: PMC8617297, DOI: 10.1038/s41467-021-27245-0.Peer-Reviewed Original ResearchConceptsBrain injuryPeripheral macrophage infiltrationIschemic brain injuryAnti-inflammatory responseMajority of astrocytesNeurite outgrowth inhibitory proteinIschemic strokePeripheral macrophagesReactive astrocytesMacrophage infiltrationStroke recoveryAstrocyte clustersMarmoset monkeysVisual cortexAstrocytesNogoASingle-nucleus transcriptomicsInhibitory proteinInjuryStrokeHuman brainInfiltrationCritical rolePrecise functionOligodendrocytesOptic 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
Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging
Sadasivam P, Fang XT, Toyonaga T, Lee S, Xu Y, Zheng MQ, Spurrier J, Huang Y, Strittmatter SM, Carson RE, Cai Z. Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular Imaging And Biology 2020, 23: 372-381. PMID: 33258040, PMCID: PMC8105262, DOI: 10.1007/s11307-020-01567-9.Peer-Reviewed Original ResearchConceptsBrain stemAlzheimer's diseaseMin postinjectionAnimal modelsAPP/PS1 miceReference regionStandardized uptake value ratioDynamic PET imaging dataUptake value ratioRodent brain tissueStatic PET scansDifferent imaging windowsPET imaging dataWild-type controlsReference tissue modelPS1 miceAD pathogenesisTherapeutic effectMouse modelRodent modelsLittermate controlsPET scansRodent brainPreclinical imaging studiesTherapeutic drug efficacyNogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury
Wang X, Zhou T, Maynard GD, Terse PS, Cafferty WB, Kocsis JD, Strittmatter SM. Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury. Brain 2020, 143: 1697-1713. PMID: 32375169, PMCID: PMC7850069, DOI: 10.1093/brain/awaa116.Peer-Reviewed Original ResearchConceptsPrimate spinal cord injurySpinal cord injuryCord injuryFemale African green monkeysTreatment-related adverse eventsChronic neurological deficitsNogo receptor 1Left motor cortexRecovery of functionPreclinical rodent modelsSpinal cord injury animalsAfrican green monkeysRaphespinal fibersAdverse eventsCervical cordNeurological deficitsSurgical complicationsCNS traumaTreatment cessationCorticospinal axonsLumbar catheterInjury animalsNeural recoverySpontaneous feedingLateral hemisectionPET 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
2019
A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration
Sekine Y, Lindborg JA, Strittmatter SM. A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration. Journal Of Biological Chemistry 2019, 295: 2175-2183. PMID: 31748413, PMCID: PMC7039549, DOI: 10.1074/jbc.ra119.009896.Peer-Reviewed Original ResearchConceptsMembrane-associated proteinsRecombinant protein expressionMatrix-associated proteinOligodendrocyte plasma membraneProteolytic C-terminal fragmentsRegeneration assaysC-terminal fragmentPlasma membraneNeurite outgrowth inhibitor NogoAxonal regenerationExosomal releaseDiffusible inhibitorC-terminalSiRNA knockdownCleavage siteCultured cellsLong fragmentPrimary cortical neuron culturesCentral nervous system traumaExosomesEnzyme inhibitor treatmentExosomal fractionSpinal cord crush injuryCerebral cortex neuronsProteinIn Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease
Toyonaga T, Smith LM, Finnema SJ, Gallezot JD, Naganawa M, Bini J, Mulnix T, Cai Z, Ropchan J, Huang Y, Strittmatter SM, Carson RE. In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease. Journal Of Nuclear Medicine 2019, 60: 1780-1786. PMID: 31101744, PMCID: PMC6894376, DOI: 10.2967/jnumed.118.223867.Peer-Reviewed Original ResearchConceptsAPP/PS1 micePS1 miceAlzheimer's diseaseWT miceSynaptic densityC-UCBDrug washoutTreatment effectsPresenilin 1 (PS1) double transgenic miceHippocampal synaptic densityAPP/PS1Double transgenic miceEnd of treatmentWild-type miceAmyloid precursor proteinEarly Alzheimer's diseaseSignificant differencesSUVR-1New PET tracersMild cognitive impairmentAD miceSynaptic deficitsOral gavageAD treatmentHealthy subjectsLimiting Neuronal Nogo Receptor 1 Signaling during Experimental Autoimmune Encephalomyelitis Preserves Axonal Transport and Abrogates Inflammatory Demyelination
Lee JY, Kim MJ, Thomas S, Oorschot V, Ramm G, Aui PM, Sekine Y, Deliyanti D, Wilkinson-Berka J, Niego B, Harvey AR, Theotokis P, McLean C, Strittmatter SM, Petratos S. Limiting Neuronal Nogo Receptor 1 Signaling during Experimental Autoimmune Encephalomyelitis Preserves Axonal Transport and Abrogates Inflammatory Demyelination. Journal Of Neuroscience 2019, 39: 5562-5580. PMID: 31061088, PMCID: PMC6616297, DOI: 10.1523/jneurosci.1760-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAxonal TransportAxonsCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalFemaleHumansIntercellular Signaling Peptides and ProteinsKinesinsMaleMiceMice, Inbred C57BLMiddle AgedMyelin SheathNerve Tissue ProteinsNogo Receptor 1Retinal Ganglion CellsSignal TransductionConceptsExperimental autoimmune encephalomyelitisCollapsin response mediator protein 2Optic nerveAxonal degenerationMultiple sclerosisAxonal vesicular transportAutoimmune encephalomyelitisInflammatory demyelinationAxonal integritySeverity of EAECre deletionAxonal transportRetinal ganglion cell axonsAxonal motor proteinsEAE-induced miceImmune-mediated destructionProgressive multiple sclerosisNeuron-specific deletionNogo receptor 1Ganglion cell axonsAnterograde transportFlx/Response mediator protein 2Adeno-associated virus serotype 2Phosphorylation of CRMP2Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance
Smith LM, Kostylev MA, Lee S, Strittmatter SM. Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance. Journal Of Biological Chemistry 2019, 294: 6042-6053. PMID: 30787106, PMCID: PMC6463724, DOI: 10.1074/jbc.ra118.006252.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD brainLeukocyte immunoglobulin-like receptorsNogo receptor 1Human AD brainsImmunoglobulin-like receptorsB member 2Brains of individualsReceptor candidatesSoluble AβOsDisease relevanceCell surface expressionHippocampal neuronsMouse modelSynthetic AβAβO bindingMemory impairmentReceptor 1Cellular prion proteinNeuronal synapsesNgR1Molecular pathologyAβAβ speciesMember 2Pyk2 Signaling through Graf1 and RhoA GTPase Is Required for Amyloid-β Oligomer-Triggered Synapse Loss
Lee S, Salazar SV, Cox TO, Strittmatter SM. Pyk2 Signaling through Graf1 and RhoA GTPase Is Required for Amyloid-β Oligomer-Triggered Synapse Loss. Journal Of Neuroscience 2019, 39: 1910-1929. PMID: 30626696, PMCID: PMC6407289, DOI: 10.1523/jneurosci.2983-18.2018.Peer-Reviewed Original ResearchConceptsDendritic spine lossGenetic variationRhoA GTPaseSynapse lossSpine lossBiochemical basisGTPase-activating proteinsFocal adhesion kinasePyk2 functionPyk2 tyrosine kinasePostsynaptic sitesTyrosine kinase Pyk2Disease riskKinase-dependent mechanismOverexpression of Pyk2Dendritic spine densityAdhesion kinaseTransgenic mouse modelBiochemical isolationPyk2 kinaseAlzheimer's disease riskDendritic spine stabilityKinase Pyk2Late-onset Alzheimer's disease (LOAD) riskActin control
2018
Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss
Salazar SV, Cox TO, Lee S, Brody AH, Chyung AS, Haas LT, Strittmatter SM. Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss. Journal Of Neuroscience 2018, 39: 758-772. PMID: 30518596, PMCID: PMC6343652, DOI: 10.1523/jneurosci.1873-18.2018.Peer-Reviewed Original ResearchConceptsTransgenic AD model miceAD model miceAbsence of Pyk2Synaptic dysfunctionModel miceHippocampal slicesSynaptic transmissionAlzheimer's diseaseAmyloid-β plaque pathologyHippocampal Schaffer collateral pathwayDisease riskLearning/memory deficitsDeletion of Pyk2Suppression of LTPBasal synaptic transmissionLate-onset Alzheimer's diseaseImpairment of learningSchaffer collateral pathwayAD-related synaptic dysfunctionAlzheimer's disease riskLate-onset Alzheimer's disease (LOAD) riskOnset Alzheimer's diseaseAge-dependent lossMechanism of actionSynaptic LTDHuman neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit
Dell’Anno M, Wang X, Onorati M, Li M, Talpo F, Sekine Y, Ma S, Liu F, Cafferty WBJ, Sestan N, Strittmatter SM. Human neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit. Nature Communications 2018, 9: 3419. PMID: 30143638, PMCID: PMC6109094, DOI: 10.1038/s41467-018-05844-8.Peer-Reviewed Original ResearchConceptsHuman neuroepithelial stem cellsNeuroepithelial stem cellsSpinal cord injury recoverySpinal cord injury resultsNeural stem cell transplantationStem cell transplantationSpinal cord repairOptimal cell typeStem cellsGrafted neuronsPersistent disabilityFunctional recoveryTherapeutic optionsCell transplantationHost axonsInjury resultsSpinal cordRobust engraftmentImmunodeficient miceInjury recoveryAnatomical sitesNeural elementsSpecific marker proteinsTransplantationAdherent conditionsWhole-Exome Sequencing of an Exceptional Longevity Cohort
Nygaard HB, Erson-Omay EZ, Wu X, Kent BA, Bernales CQ, Evans DM, Farrer MJ, Vilariño-Güell C, Strittmatter SM. Whole-Exome Sequencing of an Exceptional Longevity Cohort. The Journals Of Gerontology Series A 2018, 74: 1386-1390. PMID: 29750252, PMCID: PMC6696723, DOI: 10.1093/gerona/gly098.Peer-Reviewed Original ResearchConceptsGenetic basisRare protein-altering variantsSearch of genesGene burden analysisProtein-altering variantsIndividual genesWhole-exome sequencingAlzheimer's diseaseAging phenotypesGenesRisk variantsGenetic variantsGenetic contributionExceptional longevityExome sequencingLongevity cohortBurden analysisRare variantsNeurodegenerative disordersSequencingPhenotypeLongevityNominal statistical significanceVariantsMDN1Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration
Sekine Y, Lin-Moore A, Chenette DM, Wang X, Jiang Z, Cafferty WB, Hammarlund M, Strittmatter SM. Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration. Cell Reports 2018, 23: 415-428. PMID: 29642001, PMCID: PMC5937716, DOI: 10.1016/j.celrep.2018.03.058.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCaenorhabditis elegansCaenorhabditis elegans ProteinsCentral Nervous SystemFemaleGene Regulatory NetworksGenomeMiceMice, Inbred C57BLMice, KnockoutNerve RegenerationOptic NerveRab GTP-Binding ProteinsRecovery of FunctionRetinal Ganglion CellsRNA InterferenceRNA, Small InterferingSpinal Cord InjuriesSuppressor of Cytokine Signaling ProteinsConceptsAxonal regenerationCentral nervous system axonal regenerationRetinal ganglion cell axon regenerationGreater motor functionOptic nerve crushCerebral cortical neuronsSpinal cord traumaNeurological recoveryCord traumaNerve crushCNS injuryAxonal regrowthCortical neuronsMotor functionAxon regenerationReceptor bindingComprehensive functional screenAdult mammalsInjuryMultiple pathwaysExpression profilesIdentifies pathwaysSignificant overlapPathwayFunction screen
2017
Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS
Hirokawa T, Zou Y, Kurihara Y, Jiang Z, Sakakibara Y, Ito H, Funakoshi K, Kawahara N, Goshima Y, Strittmatter SM, Takei K. Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS. Scientific Reports 2017, 7: 12119. PMID: 28935984, PMCID: PMC5608707, DOI: 10.1038/s41598-017-12449-6.Peer-Reviewed Original ResearchConceptsSpinal cord injuryOptic nerve crushAxonal regenerationMotor recoveryNerve crushNeural repairRetinal ganglion cell axonal regenerationAdult mammalian central nervous systemIntrinsic motor recoverySpontaneous neural repairAxonal growth inhibitorsMammalian central nervous systemCentral nervous systemNon-permissive environmentLevel of functionUntreated miceFunctional recoveryCord injuryReceptor antagonistNeuronal overexpressionNervous systemGenetic deletionViral overexpressionCrushInhibitors