The Notch signaling pathway: its role in focal CNS demyelination and apotransferrin-induced remyelination
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Updated: May 7, 2026
Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
Published on: March 26, 2015
Evangelina Aparicio1, Patricia Mathieu, Milagros Pereira Luppi
1Department of Biological Chemistry, IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD, Buenos Aires, Argentina.
Abstract:
Oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Identifying the signaling pathways involved in myelin repair through oligodendroglial progenitor maturation is essential for the development of new therapies. This article investigated the role of the Notch signaling pathway in CNS demyelination and apotransferrin-induced remyelination in a focal lysolecithin-induced demyelination model in rats. Notch was found activated in Nestin-expressing neural progenitor cells and in NG2-expressing oligodendroglial precursor cells in the subventricular zone and corpus callosum of lysolecithin-demyelinated rats. Notch activation seemed to be driven by Jagged1, which led to a high expression of downstream gene Hes5 in the subventricular zone of demyelinated rats. Apotransferrin injection induced remyelination, while the injection of the γ-secretase inhibitor reversed this effect. In addition, 24 h after apotransferrin injection, evidence showed Notch activation concomitantly with an increase in F3/contactin levels and the up-regulation of the myelin-associated glycoprotein gene in the subventricular zone and corpus callosum of demyelinated rats. Collected evidence supports the participation of both canonical and non-canonical Notch signaling pathways in demyelination/remyelination. Notch activation was found to trigger Hes5 expression as a consequence of focal demyelination, which might promote oligodendroglial precursor cell proliferation. During apotransferrin-induced remyelination, Notch activation seemed to be mediated by the expression of F3/contactin, which might induce apotransferrin-mediated oligodendroglial maturation. Evidence of the participation of Notch signaling in the demyelination/remyelination process will help further understand demyelinating disorders such as Multiple Sclerosis and the use of aTf should be taken into consideration as a possible therapeutic intervention.
Insights
The Notch signaling pathway is crucial for myelin repair in the central nervous system (CNS). This study shows Notch activation promotes oligodendrocyte precursor cell proliferation and maturation, aiding remyelination in demyelinating disorders.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Demyelination and oligodendroglial damage are hallmarks of white matter and neurodegenerative diseases.
- Understanding myelin repair mechanisms, particularly oligodendroglial progenitor maturation, is key for developing new therapies.
Purpose of the Study:
- To investigate the role of the Notch signaling pathway in central nervous system (CNS) demyelination and apotransferrin-induced remyelination.
- To explore the molecular mechanisms underlying Notch pathway activation during demyelination and its impact on oligodendrocyte precursor cells.
Main Methods:
- Utilized a focal lysolecithin-induced demyelination model in rats.
- Examined Notch pathway activation in neural progenitor cells and oligodendroglial precursor cells.
- Assessed the effects of apotransferrin injection and γ-secretase inhibitor on remyelination and Notch signaling.
Main Results:
- Notch signaling was activated in progenitor and precursor cells in demyelinated areas.
- Jagged1-mediated Notch activation led to Hes5 expression, potentially promoting precursor cell proliferation.
- Apotentransferrin induced remyelination, associated with Notch activation and increased F3/contactin and myelin-associated glycoprotein gene expression.
Conclusions:
- Both canonical and non-canonical Notch signaling pathways participate in demyelination and remyelination processes.
- Notch activation influences oligodendroglial precursor cell proliferation and maturation, suggesting therapeutic potential for apotransferrin in demyelinating disorders like Multiple Sclerosis.
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