N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination
| Autor: | Linyin Feng, Limin Zeng, Gang Cheng, Qing Wang, Lei Zhang, Youhong Hu, Mengxue Zhao, Xue-li Yu, Yu Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Time Factors Notch signaling pathway lcsh:Medicine Cuprizone 03 medical and health sciences Myelin 0302 clinical medicine medicine Animals Remyelination lcsh:Science Cells Cultured Myelin Sheath Multidisciplinary Dose-Response Relationship Drug biology Multiple sclerosis lcsh:R Experimental autoimmune encephalomyelitis Oligodendrocyte differentiation Cell Differentiation Myelin Basic Protein medicine.disease Rats Myelin basic protein Cell biology Disease Models Animal Oligodendroglia 030104 developmental biology medicine.anatomical_structure nervous system Quinazolines biology.protein lcsh:Q Signal transduction 030217 neurology & neurosurgery Demyelinating Diseases Signal Transduction |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-32326-0 |
| Popis: | Oligodendrocytes are a type of glial cells that ensheath multiple neuronal axons and form myelin. Under pathological conditions, such as multiple sclerosis (MS), inflammatory damage to myelin and oligodendrocytes leads to demyelination. Although the demyelinated regions can partially resolve functional deficits through remyelination, however, as the disease progresses, remyelination typically becomes incomplete and ultimately fails. One possible explanation for this failure is the activation of the Notch pathway in MS lesions, which impedes oligodendrocyte precursor cells (OPCs) at maturation. This leads to a potential target for remyelination. Here, we have identified a compound Yhhu4952 that promoted the maturation of cultured OPCs in a dose-dependent and time-dependent manner. Neonatal rats showed a significant increase in the expression of myelin basic protein (MBP) and the prevalence of mature oligodendrocytes in the corpus callosum after Yhhu4952 treatment. The compound was also effective in promoting remyelination in cuprizone-induced demyelination model and improving severity scores in experimental autoimmune encephalomyelitis (EAE) model. Mechanism studies revealed that Yhhu4952 promotes OPC differentiation through the inhibition of the Jagged1-Notch1 pathway. These findings suggest Yhhu4952 is potentially useful for proceeding oligodendrocyte differentiation and remyelination. |
| Databáze: | OpenAIRE |
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