ArticleThe EMBO journal2020
ADAM17-triggered TNF signalling protects the ageing Drosophila retina from lipid droplet-mediated degeneration.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- The Eye as a Window to Neurodegeneration: Oxidative Stress, Optic Nerve Vulnerability, and Retinal Biomarkers-A Scoping Review.Antioxidants (Basel, Switzerland) · 2026Review
- iRhom2 deletion protects against diabetic neuropathy by suppressing neuroinflammation.The Journal of pharmacology and experimental therapeutics · 2026Article
- Age- and Genotype-Associated Specific Expression of IL-1 and TNF Receptors on Immunocompetent Cells.International journal of molecular sciences · 2026Article
- Microglial Feimin Alleviates Cognitive Impairment in High-Fat Diet-Fed Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- High-fat diet alters retinal lipid composition and gene expression networks in mice.BMC biology · 2025Article
- Wengen's hidden powers: ROS triggers a TNFR-dependent tissue regenerative pathway in Drosophila.The EMBO journal · 2024Article
- The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective.Biomolecules · 2023Review
- A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity.Cellular and molecular life sciences : CMLS · 2023Article
- Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light-induced damage in Drosophila.PLoS genetics · 2023Article
- Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy.Frontiers in molecular neuroscience · 2023Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- The Autism Spectrum Disorder-Associated Bacterial MetaboliteInternational journal of molecular sciences · 2022Article
- 'Fly-ing' from rare to common neurodegenerative disease mechanisms.Trends in genetics : TIG · 2022Review
- Identification of the extracellular metallo-endopeptidases ADAM and ADAMTS in the yellow fever mosquito Aedes aegypti.Insect biochemistry and molecular biology · 2022Article
- Role of aging in Blood-Brain Barrier dysfunction and susceptibility to SARS-CoV-2 infection: impacts on neurological symptoms of COVID-19.Fluids and barriers of the CNS · 2022Review
- SEED LIPID DROPLET PROTEIN1, SEED LIPID DROPLET PROTEIN2, and LIPID DROPLET PLASMA MEMBRANE ADAPTOR mediate lipid droplet-plasma membrane tethering.The Plant cell · 2022Article
- Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system.Frontiers in immunology · 2022Review
- Functions of Stress-Induced Lipid Droplets in the Nervous System.Frontiers in cell and developmental biology · 2022Review
- Non-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury.Nature communications · 2021Article
- Adipose triglyceride lipase protects renal cell endocytosis in a Drosophila dietary model of chronic kidney disease.PLoS biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Animals have evolved multiple mechanisms to protect themselves from the cumulative effects of age-related cellular damage. Here, we reveal an unexpected link between the TNF (tumour necrosis factor) inflammatory pathway, triggered by the metalloprotease ADAM17/TACE, and a lipid droplet (LD)-mediated mechanism of protecting retinal cells from age-related degeneration. Loss of ADAM17, TNF and the TNF receptor Grindelwald in pigmented glial cells of the Drosophila retina leads to age-related degeneration of both glia and neurons, preceded by an abnormal accumulation of glial LDs. We show that the glial LDs initially buffer the cells against damage caused by glial and neuronally generated reactive oxygen species (ROS), but that in later life the LDs dissipate, leading to the release of toxic peroxidated lipids. Finally, we demonstrate the existence of a conserved pathway in human iPS-derived microglia-like cells, which are central players in neurodegeneration. Overall, we have discovered a pathway mediated by TNF signalling acting not as a trigger of inflammation, but as a cytoprotective factor in the retina.
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Registered trials
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