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.

The expression patterns of the seven members of the ADAM (a disintegrin and metalloprotease) family, ADAM9, ADAM10, ADAM12, ADAM13, ADAM17, ADAM22, and ADAM23 were analyzed in the developing chicken retina by in situ hybridization and immunohistochemistry. Results show that each individual ADAM is expressed and regulated spatiotemporally in the developing retinal layers. ADAM9, ADAM10 and ADAM17 are widely expressed in the differential layers of the retina throughout the whole embryonic period, while ADAM12 and ADAM13 are mainly expressed in the ganglion cell layer at a later stage. ADAM22 and ADAM23 are restricted to the inner nuclear layer and the ganglion cell layer at a later stage. Furthermore, ADAM10 protein is co‐expressed with the four members of the classic cadherins, N‐cadherin, R‐cadherin, cadherin‐6B and cadherin‐7 in distinct retinal layers. Therefore, the differential expression of the investigated ADAMs in the developing retina suggests the contribution of them to the retina development.

ADAM23 is widely expressed in the embryonic central nervous system and plays an important role in tissue formation. In this study, we showed that ADAM23 contributes to cell survival and is involved in neuronal differentiation during the differentiation of human neural progenitor cells (hNPCs). Upregulation of ADAM23 in hNPCs was found to increase the number of neurons and the length of neurite, while its downregulation decreases them and triggers cell apoptosis. RNA microarray analysis revealed mechanistic insights into genes and pathways that may become involved in multiple cellular processes upon up- or downregulation of ADAM23. Our results suggest that ADAM23 regulates neuronal differentiation by triggering specific signaling pathways during hNPC differentiation.