Cited by 55Phagocytosis and Immune RegulationAutophagy in Disease and TherapyGenetics, Aging, and Longevity in Model Organisms

Defective Phagocytic Corpse Processing Results in Neurodegeneration and Can Be Rescued by TORC1 Activation

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Etchegaray, Jon Iker, Elguero, Emma J., Tran, Jennifer A., Sinatra, Vincent, Feany, Mel B., McCall, Kimberly·2016·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.1912-15.2016

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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
Published
2016-03-16
Volume
36
Issue
11
Pages
3170-3183
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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

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