Project R-15606

Timely wrapping of myelin in the PNS: unraveling the role of a new factor in health and disease (Research)

In the peripheral nervous system (PNS), immature Schwann cells (SCs) differentiate to initiate myelin synthesis, which ensures proper nerve conduction. In peripheral neuropathies, such as Charcot-Marie-Tooth disease type 1A (CMT1A), this process is disturbed due to SC dedifferentiation and, consequently, results in dysmyelination. We have recently identified a new trophic factor as highly important for myelination of the central NS. However, to date, the function of this factor in the PNS has yet to be elucidated. In this project, we combine state-of-the-art experimental tools, including in vivo SC tracer experiments, unbiased omics approaches, and patient-derived in vitro models to provide new insights into the function of the factor in SC biology and PNS myelination in health and disease. First, the involvement in PNS myelinogenesis is determined, by zooming in on SC functions and identifying underlying pathways. The second part focuses on investigating whether this factor is also an important player in CMT1A, and is able to restore dysfunctional SCs present in these patients to boost repair. In sum, this project will provide better insights into the biology of this new factor in the context of PNS myelination and contribute to new treatment approaches for PNS disease.

01 January 2025 - 31 December 2028