ADAM17 Regulates p75NTR-Mediated Fibrinolysis and Nerve Remyelination

We previously reported that a-disintegrin and metalloproteinase (ADAM)17 is a key protease regulating myelin formation. We now describe a role for ADAM17 during the Wallerian degeneration (WD) process. Unexpectedly, we observed that glial ADAM17, by regulating p75(NTR) processing, cell autonomously promotes remyelination, while neuronal ADAM17 is dispensable. Accordingly, p75(NTR) abnormally accumulates specifically when ADAM17 is maximally expressed leading to a downregulation of tissue plasminogen activator (tPA) expression, excessive fibrin accumulation over time, and delayed remyelination. Mutant mice also present impaired macrophage recruitment and defective nerve conduction velocity (NCV). Thus, ADAM17 expressed in Schwann cells, controls the whole WD process, and its absence hampers effective nerve repair. Collectively, we describe a previously uncharacterized role for glial ADAM17 during nerve regeneration. Based on the results of our study, we posit that, unlike development, glial ADAM17 promotes remyelination through the regulation of p75(NTR)-mediated fibrinolysis.

Automated summary

ADAM17 in glial cells plays a crucial role in nerve regeneration by promoting remyelination through regulating p75(NTR). Its absence hampers effective nerve repair.