Human OLIG1 blocking peptide

Niemann-Pick Type C (NPC) disease is a rare neurovisceral disorder caused by mutations of either NPC1 or NPC2 gene and characterized by defective intracellular transport of cholesterol and glycosphingolipids, leading to neuron loss and myelin aberration in the central nervous system. In this study, by comparing protein expression in the cortical white matter tracts from mice at different postnatal days, we identified that in the NPC1 mutant (NPC1(-/-)) mice, the onset of myelination is delayed and the amount of the major myelin protein MBP and PLP, and oligodendrocyte regulatory factor Olig1 and Olig2, but not NG2 and Sox10, decreased significantly, suggesting a disruption of oligodendrocyte differentiation. Furthermore, in in vitro oligodendrocyte cultivation, NPC1(-/-) oligodendrocytes showed less response to the stimulation of neuron-conditioned medium (CdM), indicating a defect of oligodendrocyte per se. Interestingly, lovastatin restores the number of mature myelin forming oligodendrocytes by increasing Olig1 and Olig2 expressions. Our data suggest a potential strategy for improving myelination using lovastatin in NPC disease.

In the central nervous system (CNS), oligodendrocytes are the glial element in charge of myelin formation. Obtaining an overall presence of oligodendrocyte precursor cells/oligodendrocytes (OPCs/OLs) in culture from different sources of NSCs is an important research area, because OPCs/OLs may provide a promising therapeutic strategy for diseases affecting myelination of axons. The present study was designed to differentiate human olfactory bulb NSCs (OBNSCs) into OPCs/OLs and using expression profiling (RT-qPCR) gene, immunocytochemistry, and specific protein expression to highlight molecular mechanism(s) underlying differentiation of human OBNSCs into OPCs/OLs. The differentiation of OBNSCs was characterized by a simultaneous appearance of neurons and glial cells. The differentiation medium, containing cAMP, PDGFA, T3, and all-trans-retinoic acid (ATRA), promotes OBNSCs to generate mostly oligodendrocytes (OLs) displaying morphological changes, and appearance of long cytoplasmic processes. OBNSCs showed, after 5 days in OLs differentiation medium, a considerable decrease in the number of nestin positive cells, which was associated with a concomitant increase of NG2 immunoreactive cells and few O4(+)-OPCs. In addition, a significant up regulation in gene and protein expression profile of stage specific cell markers for OPCs/OLs (CNPase, Galc, NG2, MOG, OLIG1, OLIG2, MBP), neurons, and astrocytes (MAP2, -TubulinIII, GFAP) and concomitant decrease of OBNSCs pluripotency markers (Oct4, Sox2, Nestin), was demonstrated following induction of OBNSCs differentiation. Taken together, the present study demonstrate the marked ability of a cocktail of factors containing PDGFA, T3, cAMP, and ATRA, to induce OBNSCs differentiation into OPCs/OLs and shed light on the key genes and pathological pathways involved in this process.