Quantitative Microproteomics Based Characterization of the Central and Peripheral Nervous System of a Mouse Model of Krabbe Disease.
Autophagy
Inflammation
Mass Spectrometry
Mouse models
Neurobiology*
Neurodegenerative diseases*
Pathway Analysis
Protein Identification*
Quantification
TMT labeling
laser capture microdissection
Journal
Molecular & cellular proteomics : MCP
ISSN: 1535-9484
Titre abrégé: Mol Cell Proteomics
Pays: United States
ID NLM: 101125647
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
07
12
2018
revised:
15
03
2019
pubmed:
31
3
2019
medline:
22
1
2020
entrez:
31
3
2019
Statut:
ppublish
Résumé
Krabbe disease is a rare, childhood lysosomal storage disorder caused by a deficiency of galactosylceramide beta-galactosidase (GALC). The major effect of GALC deficiency is the accumulation of psychosine in the nervous system and widespread degeneration of oligodendrocytes and Schwann cells, causing rapid demyelination. The molecular mechanisms of Krabbe disease are not yet fully elucidated and a definite cure is still missing. Here we report the first in-depth characterization of the proteome of the Twitcher mouse, a spontaneous mouse model of Krabbe disease, to investigate the proteome changes in the Central and Peripheral Nervous System. We applied a TMT-based workflow to compare the proteomes of the corpus callosum, motor cortex and sciatic nerves of littermate homozygous Twitcher and wild-type mice. More than 400 protein groups exhibited differences in expression and included proteins involved in pathways that can be linked to Krabbe disease, such as inflammatory and defense response, lysosomal proteins accumulation, demyelination, reduced nervous system development and cell adhesion. These findings provide new insights on the molecular mechanisms of Krabbe disease, representing a starting point for future functional experiments to study the molecular pathogenesis of Krabbe disease. Data are available via ProteomeXchange with identifier PXD010594.
Identifiants
pubmed: 30926673
pii: S1535-9476(20)31822-3
doi: 10.1074/mcp.RA118.001267
pmc: PMC6553931
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1227-1241Informations de copyright
© 2019 Pellegrini et al.
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