Proteomics of the corpus callosum to identify novel factors involved in hypomyelinated Niemann-Pick Type C disease mice

Molecular Brain

Arndt Rolfs¹  Xiao Feng¹  Fan Yang¹  Jiankai Luo¹  Hartmut Schlüter²  Yudong Guan² 

[1] Albrecht-Kossel-Institute for Neuroregeneration, University Medical Center Rostock;Institute of Clinical Chemistry & Laboratory Medicine, University Medical Center Hamburg-Eppendorf;

关键词: Proteomics;    Corpus callosum;    Npc1;    Myelination;    Lipid transport;    Gltp;   

DOI  :  10.1186/s13041-019-0440-9

来源: DOAJ

【 摘 要 】

Abstract Hypomyelination in the central nerves system (CNS) is one of the most obviously pathological features in Niemann-Pick Type C disease (NPC), which is a rare neurodegenerative disorder caused by mutations in the NPC intracellular cholesterol transporter 1 or 2 (Npc1 or Npc2). Npc1 plays key roles in both neurons and oligodendrocytes during myelination, however, the linkage between the disturbed cholesterol transport and inhibited myelination is unrevealed. In this study, mass spectrometry (MS)-based differential quantitative proteomics was applied to compare protein composition in the corpus callosum between wild type (WT) and NPC mice. In total, 3009 proteins from both samples were identified, including myelin structural proteins, neuronal proteins, and astrocyte-specific proteins. In line to hypomyelination, our data revealed downregulation of myelin structural and indispensable proteins in Npc1 mutant mice. Notably, the reduced ceramide synthase 2 (Cers2), UDP glycosyltransferase 8 (Ugt8), and glycolipid transfer protein (Gltp) indicate the altered sphingolipid metabolism in the disease and the involvement of Gltp in myelination. The identification of most reported myelin structural proteins and proteins from other cell types advocates the use of the corpus callosum to investigate proteins in different cell types that regulate myelination.

【 授权许可】

Unknown