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Deep Proteomic Evaluation of Primary and Cell Line Motoneuron Disease Models Delineates Major Differences in Neuronal Characteristics*

Please always quote using this URN: urn:nbn:de:bvb:20-opus-120954
  • The fatal neurodegenerative disorders amyotrophic lateral sclerosis and spinal muscular atrophy are, respectively, the most common motoneuron disease and genetic cause of infant death. Various in vitro model systems have been established to investigate motoneuron disease mechanisms, in particular immortalized cell lines and primary neurons. Using quantitative mass-spectrometry-based proteomics, we compared the proteomes of primary motoneurons to motoneuron-like cell lines NSC-34 and N2a, as well as to non-neuronal control cells, at a depth ofThe fatal neurodegenerative disorders amyotrophic lateral sclerosis and spinal muscular atrophy are, respectively, the most common motoneuron disease and genetic cause of infant death. Various in vitro model systems have been established to investigate motoneuron disease mechanisms, in particular immortalized cell lines and primary neurons. Using quantitative mass-spectrometry-based proteomics, we compared the proteomes of primary motoneurons to motoneuron-like cell lines NSC-34 and N2a, as well as to non-neuronal control cells, at a depth of 10,000 proteins. We used this resource to evaluate the suitability of murine in vitro model systems for cell biological and biochemical analysis of motoneuron disease mechanisms. Individual protein and pathway analysis indicated substantial differences between motoneuron-like cell lines and primary motoneurons, especially for proteins involved in differentiation, cytoskeleton, and receptor signaling, whereas common metabolic pathways were more similar. The proteins associated with amyotrophic lateral sclerosis also showed distinct differences between cell lines and primary motoneurons, providing a molecular basis for understanding fundamental alterations between cell lines and neurons with respect to neuronal pathways with relevance for disease mechanisms. Our study provides a proteomics resource for motoneuron research and presents a paradigm of how mass-spectrometry-based proteomics can be used to evaluate disease model systems.show moreshow less

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Metadaten
Author: Daniel Hornburg, Carsten Drepper, Falk Butter, Felix Meissner, Michael Sendtner, Matthias Mann
URN:urn:nbn:de:bvb:20-opus-120954
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Neurobiologie
Language:English
Parent Title (English):Molecular & Cellular Proteomics : MCP
ISSN:1535-9484
Year of Completion:2014
Volume:13
Issue:12
Pagenumber:3410-20
Source:Molecular & Cellular Proteomics 13: 10.1074/mcp.M113.037291, 3410–3420, 2014.
DOI:https://doi.org/10.1074/mcp.M113.037291
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25193168
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Release Date:2016/02/16
Note:
This research was originally published in Molecular & Cellular Proteomics. Daniel Hornburg, Carsten Drepper, Falk Butter, Felix Meissner, Michael Sendtner, and Matthias Mann. Deep Proteomic Evaluation of Primary and Cell Line Motoneuron Disease Models Delineates Major Differences in Neuronal Characteristics*. Molecular & Cellular Proteomics. 2014; 13:3410–3420. © the American Society for Biochemistry and Molecular Biology.
EU-Project number / Contract (GA) number:259867
OpenAIRE:OpenAIRE