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Publication : Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system.

First Author  Ohno M Year  2009
Journal  Nat Neurosci Volume  12
Issue  12 Pages  1506-13
PubMed ID  19935654 Mgi Jnum  J:155532
Mgi Id  MGI:4414693 Doi  10.1038/nn.2438
Citation  Ohno M, et al. (2009) Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system. Nat Neurosci 12(12):1506-13
abstractText  Axonal maturation and myelination are essential processes for establishing an efficient neuronal signaling network. We found that nardilysin (N-arginine dibasic convertase, also known as Nrd1 and NRDc), a metalloendopeptidase enhancer of protein ectodomain shedding, is a critical regulator of these processes. Nrd1-/- mice had smaller brains and a thin cerebral cortex, in which there were less myelinated fibers with thinner myelin sheaths and smaller axon diameters. We also found hypomyelination in the peripheral nervous system (PNS) of Nrd1-/- mice. Neuron-specific overexpression of NRDc induced hypermyelination, indicating that the level of neuronal NRDc regulates myelin thickness. Consistent with these findings, Nrd1-/- mice had impaired motor activities and cognitive deficits. Furthermore, NRDc enhanced ectodomain shedding of neuregulin1 (NRG1), which is a master regulator of myelination in the PNS. On the basis of these data, we propose that NRDc regulates axonal maturation and myelination in the CNS and PNS, in part, through the modulation of NRG1 shedding.
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