Cited by 726Neurogenesis and neuroplasticity mechanismsNerve injury and regenerationAlzheimer's disease research and treatments

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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, Birchmeier, Carmen, Haass, Christian·2006·Science

DOI 10.1126/science.1132341

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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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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
ORCID: Garratt, Alistair N.
Citron, Martin
Birchmeier, Carmen
Haass, Christian
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2006-10-27
Volume: 314
Issue: 5799
Pages: 664-666
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1132341
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
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Control of Peripheral Nerve Myelination by the ß-Secretase BACE1

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