Defective Phagocytic Corpse Processing Results in Neurodegeneration and Can Be Rescued by TORC1 Activation
Open accessAbstract
The removal of apoptotic cell corpses is important for maintaining homeostasis. Previously, defects in apoptotic cell clearance have been linked to neurodegeneration. However, the mechanisms underlying this are still poorly understood. In this study, we report that the absence of the phagocytic receptor Draper in glia leads to a pronounced accumulation of apoptotic neurons in the brain of Drosophila melanogaster. These dead cells persist in the brain throughout the lifespan of the organism and are associated with age-dependent neurodegeneration. Our data indicate that corpses persist because of defective phagosome maturation, rather than recognition defects. TORC1 activation, or inhibition of Atg1, in glia is sufficient to rescue corpse accumulation as well as neurodegeneration. These results suggest that phagocytosis of apoptotic neurons by glia during development is essential for brain homeostasis in adult flies. Furthermore, it suggests that TORC1 regulates Draper-mediated phagosome maturation. SIGNIFICANCE STATEMENT Previously, defects in dead cell clearance were linked to neurodegeneration, but the exact mechanisms are not well understood. In this study, we report that the absence of an engulfment receptor leads to a pronounced accumulation of dead neurons in the brain of the fruit fly Drosophila melanogaster. These dead cells persist in the brain throughout the lifespan of the organism and are associated with age-dependent neurodegeneration. Our data indicate that corpses persist because of defective degradation of cells rather than recognition of dead cells.
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Microglia actively clear apoptotic cells, myelin and synaptic debris, axonal fragments and protein deposits from the CNS through phagocytosis.
“Microglia actively clear apoptotic cells, myelin and synaptic debris, axonal fragments and protein deposits from the CNS through phagocytosis [428–430].”
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- Authors
- Etchegaray, J. I., Elguero, E. J., Tran, J. A., Sinatra, V., Feany, M. B., & McCall, K.
- Affiliations
- Boston University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2016-03-16
- Volume
- 36
- Issue
- 11
- Pages
- 3170-3183
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4792933
- OpenAlex
- W2297627090
- Cited by
- 55
- References
- 54
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 7 · 2019: 9 · 2018: 3 · 2017: 4 · 2016: 2
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- OpenBU (Boston University) (submittedVersion)
- Funders
- National Institutes of Health (AG13846)
- National Institute on Aging (R01AG044113, P30AG013846, P30-AG13846))
- National Institute of General Medical Sciences (F31GM099425, R01GM094452)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- efferocytosis, phagocytosis, drapers, engulfment receptor, glia, phagosome maturation, TORC1, Atg1, neurodegeneration, age-related neurodegeneration, Drosophila melanogaster, brain homeostasis
- MeSH terms
- Age Factors, Animals, Brain, Drosophila melanogaster, Embryo, Nonmammalian, Gene Expression Regulation, Larva, Membrane Proteins, Nerve Degeneration, Neuroglia, Neurons, Phagocytosis, Transcription Factors, Apoptosis, Drosophila Proteins, Caenorhabditis elegans Proteins, Animals, Genetically Modified, RNA Interference, Eukaryotic Initiation Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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