000272858 001__ 272858
000272858 005__ 20241029085521.0
000272858 0247_ $$2doi$$a10.1038/s42003-024-07057-w
000272858 0247_ $$2pmid$$apmid:39438652
000272858 0247_ $$2pmc$$apmc:PMC11496662
000272858 0247_ $$2altmetric$$aaltmetric:169633235
000272858 037__ $$aDZNE-2024-01276
000272858 041__ $$aEnglish
000272858 082__ $$a570
000272858 1001_ $$aYasa, Seda$$b0
000272858 245__ $$aLoss of CLN3 in microglia leads to impaired lipid metabolism and myelin turnover.
000272858 260__ $$aLondon$$bSpringer Nature$$c2024
000272858 3367_ $$2DRIVER$$aarticle
000272858 3367_ $$2DataCite$$aOutput Types/Journal article
000272858 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1729850676_21847
000272858 3367_ $$2BibTeX$$aARTICLE
000272858 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000272858 3367_ $$00$$2EndNote$$aJournal Article
000272858 520__ $$aLoss-of-function mutations in CLN3 cause juvenile Batten disease, featuring neurodegeneration and early-stage neuroinflammation. How loss of CLN3 function leads to early neuroinflammation is not yet understood. Here, we have comprehensively studied microglia from Cln3∆ex7/8 mice, a genetically accurate disease model. Loss of CLN3 function in microglia leads to lysosomal storage material accumulation and abnormal morphology of subcellular organelles. Moreover, pathological proteomic signatures are indicative of defects in lysosomal function and abnormal lipid metabolism. Consistent with these findings, CLN3-deficient microglia are unable to efficiently turnover myelin and metabolize the associated lipids, showing defects in lipid droplet formation and cholesterol accumulation. Accordingly, we also observe impaired myelin integrity in aged Cln3∆ex7/8 mouse brain. Autophagy inducers and cholesterol-lowering drugs correct the observed microglial phenotypes. Taken together, these data implicate a cell-autonomous defect in CLN3-deficient microglia that impacts their ability to support neuronal cell health, suggesting microglial targeted therapies should be considered for CLN3 disease.
000272858 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000272858 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000272858 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000272858 650_7 $$2NLM Chemicals$$aCLN3 protein, mouse
000272858 650_7 $$2NLM Chemicals$$aMolecular Chaperones
000272858 650_2 $$2MeSH$$aAnimals
000272858 650_2 $$2MeSH$$aMicroglia: metabolism
000272858 650_2 $$2MeSH$$aMicroglia: pathology
000272858 650_2 $$2MeSH$$aMembrane Glycoproteins: metabolism
000272858 650_2 $$2MeSH$$aMembrane Glycoproteins: genetics
000272858 650_2 $$2MeSH$$aLipid Metabolism
000272858 650_2 $$2MeSH$$aMice
000272858 650_2 $$2MeSH$$aMolecular Chaperones: metabolism
000272858 650_2 $$2MeSH$$aMolecular Chaperones: genetics
000272858 650_2 $$2MeSH$$aMyelin Sheath: metabolism
000272858 650_2 $$2MeSH$$aNeuronal Ceroid-Lipofuscinoses: metabolism
000272858 650_2 $$2MeSH$$aNeuronal Ceroid-Lipofuscinoses: genetics
000272858 650_2 $$2MeSH$$aNeuronal Ceroid-Lipofuscinoses: pathology
000272858 650_2 $$2MeSH$$aMice, Knockout
000272858 650_2 $$2MeSH$$aLysosomes: metabolism
000272858 650_2 $$2MeSH$$aMice, Inbred C57BL
000272858 650_2 $$2MeSH$$aAutophagy
000272858 7001_ $$0P:(DE-2719)9003033$$aButz, Elisabeth$$b1$$udzne
000272858 7001_ $$0P:(DE-2719)2340744$$aColombo, Alessio Vittorio$$b2
000272858 7001_ $$aChandrachud, Uma$$b3
000272858 7001_ $$aMontore, Luca$$b4
000272858 7001_ $$0P:(DE-2719)9000794$$aTschirner, Sarah$$b5$$udzne
000272858 7001_ $$0P:(DE-2719)9001400$$aPrestel, Matthias$$b6$$udzne
000272858 7001_ $$00000-0003-1045-1158$$aSheridan, Steven D$$b7
000272858 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b8
000272858 7001_ $$0P:(DE-2719)9002589$$aGroh, Janos$$b9$$udzne
000272858 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b10
000272858 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b11
000272858 7001_ $$00000-0003-3114-0543$$aCotman, Susan L$$b12
000272858 773__ $$0PERI:(DE-600)2919698-X$$a10.1038/s42003-024-07057-w$$gVol. 7, no. 1, p. 1373$$n1$$p1373$$tCommunications biology$$v7$$x2399-3642$$y2024
000272858 8564_ $$uhttps://pub.dzne.de/record/272858/files/DZNE-2024-01276.pdf$$yOpenAccess
000272858 8564_ $$uhttps://pub.dzne.de/record/272858/files/DZNE-2024-01276.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000272858 909CO $$ooai:pub.dzne.de:272858$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000272858 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9003033$$aExternal Institute$$b1$$kExtern
000272858 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2340744$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000272858 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000794$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b5$$kDZNE
000272858 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001400$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b6$$kDZNE
000272858 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810938$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b8$$kDZNE
000272858 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9002589$$aExternal Institute$$b9$$kExtern
000272858 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2181459$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b10$$kDZNE
000272858 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2442036$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE
000272858 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000272858 9141_ $$y2024
000272858 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCOMMUN BIOL : 2022$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-27
000272858 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000272858 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-04-12T15:13:06Z
000272858 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-04-12T15:13:06Z
000272858 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000272858 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCOMMUN BIOL : 2022$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-27
000272858 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-27
000272858 9201_ $$0I:(DE-2719)1140003$$kAG Tahirovic$$lJuvenile Neurodegeneration$$x0
000272858 9201_ $$0I:(DE-2719)1110006$$kAG Lichtenthaler$$lNeuroproteomics$$x1
000272858 980__ $$ajournal
000272858 980__ $$aVDB
000272858 980__ $$aUNRESTRICTED
000272858 980__ $$aI:(DE-2719)1140003
000272858 980__ $$aI:(DE-2719)1110006
000272858 9801_ $$aFullTexts