Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury
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Significance: Myelin is a potent inhibitor of axon regeneration. In the central nervous system, failure to clear myelin debris after injury presents a major roadblock to recovery. In contrast, rapid myelin clearance in the peripheral nervous system (PNS) contributes to this system’s remarkable regenerative capacity, but the mechanisms involved have remained incompletely understood. In this work, we set out to identify novel mechanisms of PNS myelin clearance to generate new ideas about activating myelin clearance in the injured CNS. We provide evidence that Schwann cells, myelinating glia of the PNS, engulf myelin debris using two receptors, Axl and Mertk. We hypothesize that astrocytes have the potential to use this same mechanism to engulf myelin debris after CNS injury.
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After nerve injury, Schwann cells oversee the capture of myelin debris in autophagosomes in a process termed myelinophagy.
“After nerve injury, Schwann cells oversee the capture of myelin debris in autophagosomes in a process termed “myelinophagy” [459,462,463],”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [462]
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- Authors
- Brosius Lutz, A., Chung, W.-S., Sloan, S. A., Carson, G. A., Zhou, L., Lovelett, E., Posada, S., Zuchero, J. B., & Barres, B. A.
- Affiliations
- Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5125;
- Korea Advanced Institute of Science and Technology (KR)
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-09-05
- Volume
- 114
- Issue
- 38
- Pages
- E8072-E8080
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5617301
- OpenAlex
- W2752650605
- Cited by
- 225
- References
- 41
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 23 · 2023: 27 · 2022: 30 · 2021: 35 · 2020: 29 · 2019: 22 · 2018: 19
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (none)
- Christopher and Dana Reeve Foundation (none)
- HHS | National Institutes of Health (EY11310, NIH NS069375, NIH 1S10RR02678001, NIH S10 Shared Instrument Grant S10RR027431-01)
- Stanford Medical Scientist Training Program (none)
- Developmental and Neonatal Biology Training Program (NIH T32 HD007249)
- National Multiple Sclerosis Society (none)
- National Research Foundation of Korea (NRF-2016M3C7A1905391, NRF-2016R1C1B3006969)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Schwann cells, myelin debris clearance, TAM receptors, AXL, MERTK, phagocytosis, autophagy, peripheral nerve injury, nerve crush injury, macrophages, central nervous system regeneration, astrocytes, myelin debris
- MeSH terms
- c-Mer Tyrosine Kinase, Axl Receptor Tyrosine Kinase, Animals, Autophagy, Disease Models, Animal, Myelin Sheath, Phagocytosis, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Mice, Peripheral Nerve Injuries
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