Featured Publications
PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases
Zhao X, Lin Y, Liou B, Fu W, Jian J, Fannin V, Zhang W, Setchell K, Grabowski G, Sun Y, Liu C. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 120: e2210442120. PMID: 36574647, PMCID: PMC9910439, DOI: 10.1073/pnas.2210442120.Peer-Reviewed Original ResearchConceptsBlood-brain barrierParkinson's diseaseGaucher diseasePGRN deficiencyPD-like phenotypesRelevant mouse modelRare lysosomal storage diseaseCommon neurodegenerative disorderVisceral symptomsNeurobehavioral deficitsSevere neuroinflammationPD pathologyLysosomal storage diseaseTherapeutic studiesMouse modelNeuronopathic involvementProgranulinImpaired autophagyNeurodegenerative disordersGD phenotypeEarly onsetMiceDiseaseFirst linePathologyProgranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease
Jian J, Tian Q, Hettinghouse A, Zhao S, Liu H, Wei J, Grunig G, Zhang W, Setchell K, Sun Y, Overkleeft H, Chan G, Liu C. Progranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease. EBioMedicine 2016, 13: 212-224. PMID: 27789271, PMCID: PMC5264254, DOI: 10.1016/j.ebiom.2016.10.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDisease Models, AnimalFibroblastsGaucher DiseaseGlucosylceramidaseHSP70 Heat-Shock ProteinsHumansIntercellular Signaling Peptides and ProteinsLysosome-Associated Membrane GlycoproteinsLysosomesMiceMice, KnockoutPhenotypeProgranulinsProtein AggregatesProtein BindingRecombinant ProteinsStress, PhysiologicalConceptsGaucher diseaseLysosomal storage diseaseStorage diseaseCommon lysosomal storage diseaseNew therapeutic interventionsΒ-glucocerebrosidaseProgranulin insufficiencyAnimal modelsTherapeutic interventionsDiseasePGRNDisease phenotypePatient fibroblastsGCaseComplex-associated proteinsLysosomal localizationHSP70Deficiency
2023
Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances
Huang G, Jian J, Liu C. Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances. Cytokine & Growth Factor Reviews 2023, 76: 142-159. PMID: 37981505, PMCID: PMC10978308, DOI: 10.1016/j.cytogfr.2023.11.001.Peer-Reviewed Original ResearchDiverse functionsRegulation of tumorigenesisChaperone activityMultiple membrane receptorsMultitude of processesGrowth factor-like moleculesExtracellular functionsNeuronal degenerative diseasesLysosomal proteinsIntricate mechanismsLysosomal functionMembrane receptorsIntracellular componentsLysosomal hydrolasesDiverse arrayLysosomal storage diseaseProteinNeural proliferationGRN geneCritical roleGrowth factorIntricate interplayRole of progranulinPathophysiological processesStorage disease
2021
Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease
Zhao X, Liberti R, Jian J, Fu W, Hettinghouse A, Sun Y, Liu C. Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal Of Molecular Medicine 2021, 99: 1639-1654. PMID: 34453183, PMCID: PMC8541919, DOI: 10.1007/s00109-021-02127-6.Peer-Reviewed Original ResearchConceptsLysosomal storage diseaseGaucher diseaseAutophagosome-lysosome fusionCommon lysosomal storage diseasePGRN deficiencyNovel therapiesAnimal modelsProgranulinLC3-IIMolecular targetsCrucial mediatorCritical moleculesStorage diseaseDiseaseAutophagic fluxC-terminal fragmentImpaired fusionPatient fibroblastsAutophagyImpairmentKey regulator
2019
Progranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases
Cui Y, Hettinghouse A, Liu C. Progranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases. Cytokine & Growth Factor Reviews 2019, 45: 53-64. PMID: 30733059, PMCID: PMC6450552, DOI: 10.1016/j.cytogfr.2019.01.002.Peer-Reviewed Original ResearchConceptsTherapeutic targetInflammatory autoimmune diseaseRare lysosomal storage diseaseCommon neurological diseasesPromising therapeutic targetPreclinical disease modelsDrug development strategiesExtracellular progranulinAutoimmune diseasesClinical trialsLysosomal storage diseaseTherapeutic strategiesNeurological diseasesKinds of diseasesProgranulinDiseaseDisease modelsStorage diseaseMultiple membrane receptorsPathological statesTissue repairMultiple diseasesLysosomal enzymesPleiotropic functionsDiverse pathological states
2018
Molecular regulations and therapeutic targets of Gaucher disease
Chen Y, Sud N, Hettinghouse A, Liu C. Molecular regulations and therapeutic targets of Gaucher disease. Cytokine & Growth Factor Reviews 2018, 41: 65-74. PMID: 29699937, PMCID: PMC8108120, DOI: 10.1016/j.cytogfr.2018.04.003.Peer-Reviewed Original ResearchConceptsGaucher diseaseHeat shock proteinsProper foldingMolecular regulationActivity of GCaseLysosomal localizationShock proteinsCommon lysosomal storage diseaseLysosomal appearanceIon channelsCalcium ion channelsLysosomal accumulationSaposin CLysosomal storage diseaseSubstrate glucosylceramideInflammatory mediatorsProinflammatory moleculesNew targetsPathogenic mechanismsTherapeutic targetGCaseNovel moleculesSmall moleculesDiseaseStorage disease
2017
Progranulin acts as a shared chaperone and regulates multiple lysosomal enzymes
Jian J, Hettinghouse A, Liu C. Progranulin acts as a shared chaperone and regulates multiple lysosomal enzymes. Genes & Diseases 2017, 4: 125-126. PMID: 28944282, PMCID: PMC5609500, DOI: 10.1016/j.gendis.2017.05.001.Peer-Reviewed Original ResearchMultiple lysosomal enzymesLysosomal enzymesE domainLysosomal enzyme cathepsin DLysosomal storage diseaseLysosomal enzyme β-glucocerebrosidaseEnzyme cathepsin DC-terminusChaperonesMolecular mechanismsChaperone moleculesEnzyme β-glucocerebrosidaseNeuronal ceroid lipofuscinosisStorage diseaseGaucher diseaseNull miceEnzymeCeroid lipofuscinosisCathepsin DGene variantsMutationsΒ-glucocerebrosidaseRole of progranulinImportant roleProgranulin