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Control of peripheral nerve myelination by the β-secretase BACE1

Authors

  • M. Willem
  • A.N. Garratt
  • B. Novak
  • M. Citron
  • S. Kaufmann
  • A. Rittger
  • B. Destrooper
  • P. Saftig
  • C. Birchmeier
  • C. Haass

Journal

  • Science

Citation

  • Science 314 (5799): 664-666

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.


DOI

doi:10.1126/science.1132341