The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Control of Peripheral Nerve Myelination by the ß-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.
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“BACE1 is highly expressed in the nervous system and contributes to additional physiological processes besides its role in AD, e.g. through neuregulin-1 cleavage in myelination and CHL1 cleavage in axon targeting [7–12].”
From Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons (2016) · cites this paper as [7]
In the citing paper
“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]
Citations
Cites
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BACE1 is the major β-secretase for generation of Aβ peptides by neurons
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Axonal Neuregulin-1 Regulates Myelin Sheath Thickness
Michailov, G. V., Sereda, M. W., Brinkmann, B. G., Fischer, T. M., Haug, B., Birchmeier, C., Role, L. W., Lai, C., Schwab, M. H., & Nave, K. (2004) · Science · doi:10.1126/science.1095862 · Cited by 940
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Research works printed but not linked: 2
- Q. Li, T. C. Sudhof, J. Biol. Chem.279, 10542 (2003).
- G. Lemke, Sci. STKE2006, pe11 (2006).
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The molecular basis of the interactions of copper metallochaperones
Aggarwal, S. (2011)
Role of Periaxin dimerization in peripheral myelination
Wu, L. M. N. (2012) · ERA
How Does N- and O-Glycosylation Affect the Formation and Accumulation of Amyloid β-Peptide?
Kitazume, S. (2011) · Trends in Glycoscience and Glycotechnology · doi:10.4052/tigg.23.161
Wang, H. (2012) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.14459
Metadata
- 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
- 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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