Cited by 727Neurogenesis and neuroplasticity mechanismsNerve injury and regenerationAlzheimer's disease research and treatments

Control of Peripheral Nerve Myelination by the ß-Secretase BACE1

Willem, Michael, Garratt, Alistair N., Novak, Bozidar, Citron, Martin, Kaufmann, Steve, Rittger, Andrea, DeStrooper, Bart, Saftig, Paul +2 more·2006·Science

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.

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Crossref · 10.1126/science.1132341

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  • Besides APP, BACE1 has other substrates that may be important for synaptic plasticity and synaptic homeostasis.

    “Besides the amyloidogenic pathway, BACE1 has other substrates that may be important for synaptic plasticity and synaptic homeostasis.”

    From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [70]

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Authors
Willem, M., Garratt, A. N., Novak, B., Citron, M., Kaufmann, S., Rittger, A., DeStrooper, B., Saftig, P., Birchmeier, C., & Haass, C.
Affiliations
  • Amgen (United States) (US)
  • Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Schillerstrasse 44, Ludwig-Maximilians-University, 80336 Munich, Germany.
Corresponding author
  • Garratt, Alistair N.
  • Haass, Christian
Venue
Science
Published
2006-10-27
Volume
314
Issue
5799
Pages
664-666
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1977688919
Cited by
703
References
43
Citations by year
2026: 12 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 16 · 2021: 26 · 2020: 29 · 2019: 29 · 2018: 31 · 2017: 35 · 2016: 50 · 2015: 39 · 2014: 47 · 2013: 52 · 2012: 55
FWCI
13.31
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lirias (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
BACE1, peripheral nerve myelination, neuregulin-1, Schwann cells, hypomyelination, axon bundling, afferent nerve fibers, ERBB2, amyloid precursor protein
MeSH terms
Alzheimer Disease, Animals, Axons, Ganglia, Spinal, Motor Neurons, Myelin Sheath, Nerve Tissue Proteins, Neurons, Afferent, Endopeptidases, Protein Processing, Post-Translational, Schwann Cells, Sciatic Nerve, Spinal Cord, Aspartic Acid Endopeptidases, Mice, Knockout, Protein Isoforms, Neuregulin-1, Mice, Amyloid Precursor Protein Secretases

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