Milošević, Ira

[["dc.bibliographiccitation.firstpage","232"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","EMBO reports"],["dc.bibliographiccitation.lastpage","9"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Pechstein, Arndt"],["dc.contributor.author","Gerth, Fabian"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Jäpel, Maria"],["dc.contributor.author","Eichhorn-Grünig, Marielle"],["dc.contributor.author","Vorontsova, Olga"],["dc.contributor.author","Bacetic, Jelena"],["dc.contributor.author","Maritzen, Tanja"],["dc.contributor.author","Shupliakov, Oleg"],["dc.contributor.author","Freund, Christian"],["dc.contributor.author","Haucke, Volker"],["dc.date.accessioned","2019-07-09T11:41:09Z"],["dc.date.available","2019-07-09T11:41:09Z"],["dc.date.issued","2015-02-01"],["dc.description.abstract","Neurotransmission involves the exo-endocytic cycling of synaptic vesicle (SV) membranes. Endocytic membrane retrieval and clathrin-mediated SV reformation require curvature-sensing and membrane-bending BAR domain proteins such as endophilin A. While their ability to sense and stabilize curved membranes facilitates membrane recruitment of BAR domain proteins, the precise mechanisms by which they are targeted to specific sites of SV recycling has remained unclear. Here, we demonstrate that the multi-domain scaffold intersectin 1 directly associates with endophilin A to facilitate vesicle uncoating at synapses. Knockout mice deficient in intersectin 1 accumulate clathrin-coated vesicles at synapses, a phenotype akin to loss of endophilin function. Intersectin 1/endophilin A1 complex formation is mediated by direct binding of the SH3B domain of intersectin to a non-canonical site on the SH3 domain of endophilin A1. Consistent with this, intersectin-binding defective mutant endophilin A1 fails to rescue clathrin accumulation at neuronal synapses derived from endophilin A1-3 triple knockout (TKO) mice. Our data support a model in which intersectin aids endophilin A recruitment to sites of clathrin-mediated SV recycling, thereby facilitating vesicle uncoating."],["dc.identifier.doi","10.15252/embr.201439260"],["dc.identifier.fs","610968"],["dc.identifier.pmid","25520322"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11737"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58362"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/242167/EU//SYNSYS"],["dc.relation.euproject","SynSys"],["dc.relation.issn","1469-3178"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Vesicle uncoating regulated by SH3-SH3 domain-mediated complex formation between endophilin and intersectin at synapses."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","27"],["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Milosevic, Ira"],["dc.date.accessioned","2019-07-09T11:45:08Z"],["dc.date.available","2019-07-09T11:45:08Z"],["dc.date.issued","2018"],["dc.description.abstract","Without robust mechanisms to efficiently form new synaptic vesicles (SVs), the tens to hundreds of SVs typically present at the neuronal synapse would be rapidly used up, even at modest levels of neuronal activity. SV recycling is thus critical for synaptic physiology and proper function of sensory and nervous systems. Yet, more than four decades after it was originally proposed that the SVs are formed and recycled locally at the presynaptic terminals, the mechanisms of endocytic processes at the synapse are heavily debated. Clathrin-mediated endocytosis, a type of endocytosis that capitalizes on the clathrin coat, a number of adaptor and accessory proteins, and the GTPase dynamin, is well understood, while the contributions of clathrin-independent fast endocytosis, kiss-and-run, bulk endocytosis and ultrafast endocytosis are still being evaluated. This review article revisits and summarizes the current knowledge on the SV reformation with a focus on clathrin-mediated endocytosis, and it discusses the modes of SV formation from endosome-like structures at the synapse. Given the importance of this topic, future advances in this active field are expected to contribute to better comprehension of neurotransmission, and to have general implications for neuroscience and medicine."],["dc.identifier.doi","10.3389/fncel.2018.00027"],["dc.identifier.pmid","29467622"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15037"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59162"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1662-5102"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Revisiting the Role of Clathrin-Mediated Endoytosis in Synaptic Vesicle Recycling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Sathyanarayanan, Udhayabhaskar"],["dc.contributor.author","Musa, Marina"],["dc.contributor.author","Bou Dib, Peter"],["dc.contributor.author","Raimundo, Nuno"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Krisko, Anita"],["dc.date.accessioned","2021-04-14T08:31:49Z"],["dc.date.available","2021-04-14T08:31:49Z"],["dc.date.issued","2020"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.1038/s41467-020-19104-1"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83720"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2041-1723"],["dc.relation.orgunit","Abteilung Experimentelle Neurodegeneration"],["dc.rights","CC BY 4.0"],["dc.title","ATP hydrolysis by yeast Hsp104 determines protein aggregate dissolution and size in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","45076"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Fernandez-Mosquera, Lorena"],["dc.contributor.author","Diogo, Catia V."],["dc.contributor.author","Yambire, King Faisal"],["dc.contributor.author","Santos, Gabriela L."],["dc.contributor.author","Luna Sanchez, Marta"],["dc.contributor.author","Benit, Paule"],["dc.contributor.author","Rustin, Pierre"],["dc.contributor.author","Carlos Lopez, Luis"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Raimundo, Nuno"],["dc.date.accessioned","2018-11-07T10:26:02Z"],["dc.date.available","2018-11-07T10:26:02Z"],["dc.date.issued","2017"],["dc.description.abstract","Mitochondria are key cellular signaling platforms, affecting fundamental processes such as cell proliferation, differentiation and death. However, it remains unclear how mitochondrial signaling affects other organelles, particularly lysosomes. Here, we demonstrate that mitochondrial respiratory chain (RC) impairments elicit a stress signaling pathway that regulates lysosomal biogenesis via the microphtalmia transcription factor family. Interestingly, the effect of mitochondrial stress over lysosomal biogenesis depends on the timeframe of the stress elicited: while RC inhibition with rotenone or uncoupling with CCCP initially triggers lysosomal biogenesis, the effect peaks after few hours and returns to baseline. Long-term RC inhibition by long-term treatment with rotenone, or patient mutations in fibroblasts and in a mouse model result in repression of lysosomal biogenesis. The induction of lysosomal biogenesis by short-term mitochondrial stress is dependent on TFEB and MITF, requires AMPK signaling and is independent of calcineurin signaling. These results reveal an integrated view of how mitochondrial signaling affects lysosomes, which is essential to fully comprehend the consequences of mitochondrial malfunction, particularly in the context of mitochondrial diseases."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1038/srep45076"],["dc.identifier.isi","000397760800001"],["dc.identifier.pmid","28345620"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14396"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42963"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Acute and chronic mitochondrial respiratory chain deficiency differentially regulate lysosomal biogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Yambire, King Faisal"],["dc.contributor.author","Rostosky, Christine"],["dc.contributor.author","Watanabe, Takashi"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Torres-Odio, Sylvia"],["dc.contributor.author","Sanchez-Guerrero, Angela"],["dc.contributor.author","Senderovich, Ola"],["dc.contributor.author","Meyron-Holtz, Esther G"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","West, A Phillip"],["dc.contributor.author","Raimundo, Nuno"],["dc.date.accessioned","2020-12-10T18:48:09Z"],["dc.date.available","2020-12-10T18:48:09Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.7554/eLife.51031"],["dc.identifier.pmid","31793879"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17114"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79035"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/104"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P02: Charakterisierung der ER-Mitochondrien-Kontakte und ihre Rolle in der Signalweiterleitung"],["dc.relation.workinggroup","RG Milosevic (Synaptic Vesicle Dynamics)"],["dc.relation.workinggroup","RG Raimundo"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","79"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Masaracchia, Caterina"],["dc.contributor.author","Hnida, Marilena"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Lopes da Fonseca, Tomás"],["dc.contributor.author","Villar-Pique, Anna"],["dc.contributor.author","Branco, Tiago"],["dc.contributor.author","Stahlberg, Markus A."],["dc.contributor.author","Dean, Camin"],["dc.contributor.author","Fernández, Claudio O."],["dc.contributor.author","Milošević, Ira"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2019-07-09T11:45:45Z"],["dc.date.available","2019-07-09T11:45:45Z"],["dc.date.issued","2018"],["dc.description.abstract","Abstract Alpha-synuclein (aSyn) plays a crucial role in Parkinson\\’s disease (PD) and other synucleinopathies, since it misfolds and accumulates in typical proteinaceous inclusions. While the function of aSyn is thought to be related to vesicle binding and trafficking, the precise molecular mechanisms linking aSyn with synucleinopathies are still obscure. aSyn can spread in a prion-like manner between interconnected neurons, contributing to the propagation of the pathology and to the progressive nature of synucleinopathies. Here, we investigated the interaction of aSyn with membranes and trafficking machinery pathways using cellular models of PD that are amenable to detailed molecular analyses. We found that different species of aSyn can enter cells and form high molecular weight species, and that membrane binding properties are important for the internalization of aSyn. Once internalized, aSyn accumulates in intracellular inclusions. Interestingly, we found that internalization is blocked in the presence of dynamin inhibitors (blocked membrane scission), suggesting the involvement of the endocytic pathway in the internalization of aSyn. By screening a pool of small Rab-GTPase proteins (Rabs) which regulate membrane trafficking, we found that internalized aSyn partially colocalized with Rab5A and Rab7. Initially, aSyn accumulated in Rab4A-labelled vesicles and, at later stages, it reached the autophagy-lysosomal pathway (ALP) where it gets degraded. In total, our study emphasizes the importance of membrane binding, not only as part of the normal function but also as an important step in the internalization and subsequent accumulation of aSyn. Importantly, we identified a fundamental role for Rab proteins in the modulation of aSyn processing, clearance and spreading, suggesting that targeting Rab proteins may hold important therapeutic value in PD and other synucleinopathies."],["dc.identifier.doi","10.1186/s40478-018-0578-1"],["dc.identifier.pmid","30107856"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15309"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59304"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/98"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/36"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P02: Charakterisierung der ER-Mitochondrien-Kontakte und ihre Rolle in der Signalweiterleitung"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration"],["dc.relation.workinggroup","RG Milosevic (Synaptic Vesicle Dynamics)"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Membrane binding, internalization, and sorting of alpha-synuclein in the cell"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","994"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Aging Cell"],["dc.bibliographiccitation.lastpage","1005"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Perić, Matea"],["dc.contributor.author","Lovrić, Anita"],["dc.contributor.author","Šarić, Ana"],["dc.contributor.author","Musa, Marina"],["dc.contributor.author","Bou Dib, Peter"],["dc.contributor.author","Rudan, Marina"],["dc.contributor.author","Nikolić, Andrea"],["dc.contributor.author","Sobočanec, Sandra"],["dc.contributor.author","Mikecin, Ana-Matea"],["dc.contributor.author","Dennerlein, Sven"],["dc.contributor.author","Milošević, Ira"],["dc.contributor.author","Vlahoviček, Kristian"],["dc.contributor.author","Raimundo, Nuno"],["dc.contributor.author","Kriško, Anita"],["dc.date.accessioned","2019-07-09T11:44:59Z"],["dc.date.available","2019-07-09T11:44:59Z"],["dc.date.issued","2017"],["dc.description.abstract","Protein quality control mechanisms, required for normal cellular functioning, encompass multiple functions related to protein production and maintenance. However, the existence of communication between proteostasis and metabolic networks and its underlying mechanisms remain elusive. Here, we report that enhanced chaperone activity and consequent improved proteostasis are sensed by TORC1 via the activity of Hsp82. Chaperone enrichment decreases the level of Hsp82, which deactivates TORC1 and leads to activation of Snf1/AMPK, regardless of glucose availability. This mechanism culminates in the extension of yeast replicative lifespan (RLS) that is fully reliant on both TORC1 deactivation and Snf1/AMPK activation. Specifically, we identify oxygen consumption increase as the downstream effect of Snf1 activation responsible for the entire RLS extension. Our results set a novel paradigm for the role of proteostasis in aging: modulation of the misfolded protein level can affect cellular metabolic features as well as mitochondrial activity and consequently modify lifespan. The described mechanism is expected to open new avenues for research of aging and age-related diseases."],["dc.identifier.doi","10.1111/acel.12623"],["dc.identifier.pmid","28613034"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14988"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59133"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","315997"],["dc.relation","316289"],["dc.relation","337327"],["dc.relation.issn","1474-9726"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","612"],["dc.title","TORC1-mediated sensing of chaperone activity alters glucose metabolism and extends lifespan."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e39598"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Yambire, King Faisal"],["dc.contributor.author","Fernandez-Mosquera, Lorena"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Mühle, Christiane"],["dc.contributor.author","Ikonen, Elina"],["dc.contributor.author","Raimundo, Nuno"],["dc.contributor.author","Milošević, Ira"],["dc.date.accessioned","2020-12-10T18:48:06Z"],["dc.date.available","2020-12-10T18:48:06Z"],["dc.date.issued","2019"],["dc.description.abstract","Perturbations in mitochondrial function and homeostasis are pervasive in lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses mitochondrial biogenesis and function in lysosomal storage diseases Niemann-Pick type C (NPC) and acid sphingomyelinase deficiency (ASM), in patient cells and mouse tissues. This mechanism is mediated by the transcription factors KLF2 and ETV1, which are both induced in NPC and ASM patient cells. Mitochondrial biogenesis and function defects in these cells are rescued by the silencing of KLF2 or ETV1. Increased ETV1 expression is regulated by KLF2, while the increase of KLF2 protein levels in NPC and ASM stems from impaired signaling downstream sphingosine-1-phosphate receptor 1 (S1PR1), which normally represses KLF2. In patient cells, S1PR1 is barely detectable at the plasma membrane and thus unable to repress KLF2. This manuscript provides a mechanistic pathway for the prevalent mitochondrial defects in lysosomal storage diseases."],["dc.identifier.doi","10.7554/eLife.39598"],["dc.identifier.pmid","30775969"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15862"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79020"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/58"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P02: Charakterisierung der ER-Mitochondrien-Kontakte und ihre Rolle in der Signalweiterleitung"],["dc.relation.eissn","2050-084X"],["dc.relation.issn","2050-084X"],["dc.relation.workinggroup","RG Milosevic (Synaptic Vesicle Dynamics)"],["dc.relation.workinggroup","RG Raimundo"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","83"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Kanata, Eirini"],["dc.contributor.author","Diaz-Lucena, Daniela"],["dc.contributor.author","Xanthopoulos, Konstantinos"],["dc.contributor.author","Kovatsi, Eleni"],["dc.contributor.author","Pleschka, Catharina"],["dc.contributor.author","Garcia-Esparcia, Paula"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Ozbay, Duru"],["dc.contributor.author","Correia, Susana"],["dc.contributor.author","Correia, Ângela"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Fernández-Borges, Natalia"],["dc.contributor.author","Vorberg, Ina M."],["dc.contributor.author","Glatzel, Markus"],["dc.contributor.author","Sklaviadis, Theodoros"],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Krasemann, Susanne"],["dc.contributor.author","Sánchez-Valle, Raquel"],["dc.contributor.author","Ferrer, Isidro"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2019-07-09T11:44:59Z"],["dc.date.available","2019-07-09T11:44:59Z"],["dc.date.issued","2017"],["dc.description.abstract","Background YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing. Methods In the present study, we comparatively analysed YKL-40 levels in the brain and CSF samples from neurodegenerative dementias of different aetiologies characterized by the presence of cortical pathology and disease-specific neuroinflammatory signatures. Results YKL-40 was normally expressed in fibrillar astrocytes in the white matter. Additionally YKL-40 was highly and widely expressed in reactive protoplasmic cortical and perivascular astrocytes, and fibrillar astrocytes in sporadic Creutzfeldt-Jakob disease (sCJD). Elevated YKL-40 levels were also detected in Alzheimer’s disease (AD) but not in dementia with Lewy bodies (DLB). In AD, YKL-40-positive astrocytes were commonly found in clusters, often around β-amyloid plaques, and surrounding vessels with β-amyloid angiopathy; they were also distributed randomly in the cerebral cortex and white matter. YKL-40 overexpression appeared as a pre-clinical event as demonstrated in experimental models of prion diseases and AD pathology. CSF YKL-40 levels were measured in a cohort of 288 individuals, including neurological controls (NC) and patients diagnosed with different types of dementia. Compared to NC, increased YKL-40 levels were detected in sCJD (p < 0.001, AUC = 0.92) and AD (p < 0.001, AUC = 0.77) but not in vascular dementia (VaD) (p > 0.05, AUC = 0.71) or in DLB/Parkinson’s disease dementia (PDD) (p > 0.05, AUC = 0.70). Further, two independent patient cohorts were used to validate the increased CSF YKL-40 levels in sCJD. Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations. Conclusions Our results unequivocally demonstrate that in neurodegenerative dementias, YKL-40 is a disease-specific marker of neuroinflammation showing its highest levels in prion diseases. Therefore, YKL-40 quantification might have a potential for application in the evaluation of therapeutic intervention in dementias with a neuroinflammatory component."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1186/s13024-017-0226-4"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14995"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59135"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15151 but duplicate"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Farsi, Zohreh"],["dc.contributor.author","Gowrisankaran, Sindhuja"],["dc.contributor.author","Krunic, Matija"],["dc.contributor.author","Rammner, Burkhard"],["dc.contributor.author","Woehler, Andrew"],["dc.contributor.author","Lafer, Eileen M"],["dc.contributor.author","Mim, Carsten"],["dc.contributor.author","Jahn, Reinhard"],["dc.contributor.author","Milosevic, Ira"],["dc.date.accessioned","2020-12-10T18:48:06Z"],["dc.date.available","2020-12-10T18:48:06Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.7554/eLife.32569"],["dc.identifier.eissn","2050-084X"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15262"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79016"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]