title: Control of peripheral nerve myelination by the beta-secretase BACE1.
abstract: Although BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) is essential for the generation of amyloid-b peptide in Alzheimer's disease, its physiological function is unclear. 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 that seen in 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, probably through processing of type III NRG1.
authors.affiliation: Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Schillerstrasse 44, Ludwig-Maximilians-University, 80336 Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Willem
authors.forename: Alistair N
authors.initials: AN
authors.lastname: Garratt
authors.forename: Bozidar
authors.initials: B
authors.lastname: Novak
authors.forename: Martin
authors.initials: M
authors.lastname: Citron
authors.forename: Steve
authors.initials: S
authors.lastname: Kaufmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Rittger
authors.forename: Bart
authors.initials: B
authors.lastname: DeStrooper
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001369:Axons / Q000502:physiology*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020890:Neuregulin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D020033:Protein Isoforms; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse