Control of peripheral nerve myelination by the β-secretase BACE1

Item Type:	Article
Title:	Control of peripheral nerve myelination by the β-secretase BACE1
Creators Name:	Willem, M. and Garratt, A.N. and Novak, B. and Citron, M. and Kaufmann, S. and Rittger, A. and Destrooper, B. and Saftig, P. and Birchmeier, C. and Haass, C.
Abstract:	Although BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) is essential for the generation of amyloid beta-peptide in Alzheimer's disease, its physiological function is unclear. Here we found that very high levels of BACE1 were expressed at time points when peripheral nerves become myelinated. Deficiency of BACE1 resulted in the accumulation of unprocessed neuregulin 1 (NRG1), an axonally expressed factor required for glial cell development and myelination. BACE1(-/-) mice displayed hypomyelination of peripheral nerves and aberrant axonal segregation of small diameter afferent fibers very similar to mice with mutations in type III NRG1, or Schwann cell-specific ErbB2 knockouts. Thus, BACE1 is required for myelination and correct bundling of axons by Schwann cells most likely via processing of type III NRG1.
Keywords:	Afferent Neurons, Alzheimer Disease, Amyloid Precursor Protein Secretases, Aspartic Acid Endopeptidases, Axons, Endopeptidases, Knockout Mice, Motor Neurons, Myelin Sheath, Nerve Tissue Proteins, Neuregulin-1, Post-Translational Protein Processing, Protein Isoforms, Schwann Cells, Sciatic Nerve, Spinal Cord, Spinal Ganglia, Animals, Mice
Source:	Science
ISSN:	0036-8075
Publisher:	American Association for the Advancement of Science
Volume:	314
Number:	5799
Page Range:	664-666
Date:	27 October 2006
Official Publication:	https://doi.org/10.1126/science.1132341
PubMed:	View item in PubMed

Repository Staff Only: item control page