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Organisms: Mus musculus, Rattus norvegicus, Homo sapiens, Macaca mulatta, Sus scrofa
Remyelination can occur naturally in demyelinating lesions, but often fails in human demyelinating diseases such as multiple sclerosis (MS). The function of the innate immune system is essential for the regenerative response, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal ...
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Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We ...
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Blood samples (20 ml) from clinically affected homozygous Npc1 mutation carriers and healthy donors were collected. Negative selection of peripheral blood monocyte-derived macrophages was performed by incubating full blood for 20 min at RT with RosetteSep Human Monocyte Enrichment Cocktail (StemCell Technologies). An equal volume of washing buffer (D-PBS/2% FBS/1 mM EDTA) was added to each sample and layer of macrophages was separated from red blood cells and plasma by centrifugation on a Ficoll ...
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Homo sapiens, Mus musculus
SOPs: No SOPs
Data files: Proteomic analysis of monocyte derived macropha..., Proteomic signature of NPC1 KO microglia, Proteomic signature of NPC1 KO microglia from c...
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Microglia isolated by MACS from WT and Myd88-/- mouse pups were seeded at a density of 1×106 cells per 60-mm dish in DMEM/FCS/L929 medium. After 2 DIV, microglia were washed with warm DMEM/pyruvate medium and treated with 20 µg/mL myelin debris (or HEPES control) in 2 mL of TIC medium for 4 h. After treatment, the cells were washed with DMEM/pyruvate medium, and incubated with 4 mL of DMEM containing 0.2% BSA for 16 h. The cells in each dish were washed with 2 mL of cold PBS on ice, and lysed ...
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Mus musculus
SOPs: No SOPs
Data files: Pro-inflammatory activity following demyelinati...
Snapshots: No snapshots
Remyelination can occur naturally in demyelinating lesions, but often fails in human demyelinating diseases such as multiple sclerosis (MS). The function of the innate immune system is essential for the regenerative response, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal ...
Creators: Rainer Malik, Stephan Müller, Stefan Lichtenthaler, Martina Fetting, Mikael Simons
Submitter: Rainer Malik
Investigations: Proteomics
Studies: Pro-inflammatory activation following demyelina...
Assays: Shotgun proteomics
Niemann-Pick type C disease is a rare neurodegenerative disorder mainly caused by mutations in Npc1, resulting in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is a prominent pathological feature, direct consequences of NPC1 loss on microglial function remain uncharacterized. Previously, we have characterized microglial proteome alterations in the NPC1 KO mouse model (PXD019447). In order to investigate similar changes in humans, we have cultured monocyte derived macrophages ...
Creators: Rainer Malik, Stefan Lichtenthaler, Stephan Müller, Mikael Simons, Martina Fetting
Submitter: Rainer Malik
Investigations: Proteomics
Studies: Loss of NPC1 enhances phagocytic uptake and imp...
Assays: Shotgun proteomics
Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We ...
Creators: Rainer Malik, Stephan Müller, Stefan Lichtenthaler, Martina Fetting, Mikael Simons
Submitter: Rainer Malik
Investigations: Proteomics
Studies: Loss of NPC1 enhances phagocytic uptake and imp...
Assays: Shotgun proteomics
Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We ...
Creators: Rainer Malik, Stefan Lichtenthaler, Stephan Müller, Mikael Simons, Martina Fetting
Submitter: Rainer Malik
Investigations: Proteomics
Studies: Loss of NPC1 enhances phagocytic uptake and imp...
Assays: Shotgun proteomics
Abstract (Expand)
Authors: D. Brenner, K. Sieverding, J. Srinidhi, S. Zellner, C. Secker, R. Yilmaz, J. Dyckow, S. Amr, A. Ponomarenko, E. Tunaboylu, Y. Douahem, J. S. Schlag, L. Rodriguez Martinez, G. Kislinger, C. Niemann, K. Nalbach, W. P. Ruf, J. Uhl, J. Hollenbeck, L. Schirmer, A. Catanese, C. S. Lobsiger, K. M. Danzer, D. Yilmazer-Hanke, C. Munch, P. Koch, A. Freischmidt, M. Fetting, C. Behrends, R. Parlato, J. H. Weishaupt
Date Published: 6th May 2024
Publication Type: Journal
PubMed ID: 38517332
Citation: J Exp Med. 2024 May 6;221(5):e20221190. doi: 10.1084/jem.20221190. Epub 2024 Mar 22.
Abstract (Expand)
Authors: S. Safaiyan, S. Besson-Girard, T. Kaya, L. Cantuti-Castelvetri, L. Liu, H. Ji, M. Schifferer, G. Gouna, F. Usifo, N. Kannaiyan, D. Fitzner, X. Xiang, M. J. Rossner, M. Brendel, O. Gokce, M. Simons
Date Published: 7th Apr 2021
Publication Type: Journal
PubMed ID: 33606969
Citation: Neuron. 2021 Apr 7;109(7):1100-1117.e10. doi: 10.1016/j.neuron.2021.01.027. Epub 2021 Feb 18.
Abstract (Expand)
Authors: A. Colombo, L. Dinkel, S. A. Muller, L. Sebastian Monasor, M. Schifferer, L. Cantuti-Castelvetri, J. Konig, L. Vidatic, T. Bremova-Ertl, A. P. Lieberman, S. Hecimovic, M. Simons, S. F. Lichtenthaler, M. Strupp, S. A. Schneider, S. Tahirovic
Date Published: 24th Feb 2021
Publication Type: Journal
PubMed ID: 33627648
Citation: Nat Commun. 2021 Feb 24;12(1):1158. doi: 10.1038/s41467-021-21428-5.
Abstract (Expand)
Authors: M. I. Cunha, M. Su, L. Cantuti-Castelvetri, S. A. Muller, M. Schifferer, M. Djannatian, I. Alexopoulos, F. van der Meer, A. Winkler, T. J. van Ham, B. Schmid, S. F. Lichtenthaler, C. Stadelmann, M. Simons
Date Published: 4th May 2020
Publication Type: Journal
PubMed ID: 32078678
Citation: J Exp Med. 2020 May 4;217(5):e20191390. doi: 10.1084/jem.20191390.