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Unaltered prion disease in mice lacking developmental endothelial locus–1


Zhu, Caihong; Li, Zhihao; Li, Bei; Pfammatter, Manuela; Hornemann, Simone; Aguzzi, Adriano (2019). Unaltered prion disease in mice lacking developmental endothelial locus–1. Neurobiology of Aging, 76:208-213.

Abstract

Progression of prion diseases is driven by the accumulation of prions in the brain. Ablation of microglia or deletion of the eat-me-signal, milk-fat globule epidermal growth factor VIII (Mfge8), accelerates prion pathogenesis, suggesting that microglia defend the brain by phagocytosing prions. Similar to Mfge8, developmental endothelial locus–1 (Del-1) is a secreted protein that acts as an opsonin bridging phagocytes and apoptotic cells to facilitate phagocytosis. We therefore asked whether Del-1 might play a role in controlling prion pathogenesis. We assessed the anti-inflammatory and phagocytosis-promoting functions of Del-1 in prion disease and determined whether Del-1 complements Mfge8 in prion clearance in mice with a C57BL/6J genetic background. We found that Del-1 deficiency did not change prion disease progression or lesion patterns. In addition, prion clearance and scrapie prion protein deposition were unaltered in Del-1–deficient mice. In addition, prion-induced neuroinflammation was not affected by Del-1 deficiency. We conclude that Del-1 is not a major determinant of prion pathogenesis in this context.

Abstract

Progression of prion diseases is driven by the accumulation of prions in the brain. Ablation of microglia or deletion of the eat-me-signal, milk-fat globule epidermal growth factor VIII (Mfge8), accelerates prion pathogenesis, suggesting that microglia defend the brain by phagocytosing prions. Similar to Mfge8, developmental endothelial locus–1 (Del-1) is a secreted protein that acts as an opsonin bridging phagocytes and apoptotic cells to facilitate phagocytosis. We therefore asked whether Del-1 might play a role in controlling prion pathogenesis. We assessed the anti-inflammatory and phagocytosis-promoting functions of Del-1 in prion disease and determined whether Del-1 complements Mfge8 in prion clearance in mice with a C57BL/6J genetic background. We found that Del-1 deficiency did not change prion disease progression or lesion patterns. In addition, prion clearance and scrapie prion protein deposition were unaltered in Del-1–deficient mice. In addition, prion-induced neuroinflammation was not affected by Del-1 deficiency. We conclude that Del-1 is not a major determinant of prion pathogenesis in this context.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Developmental Biology, Ageing, General Neuroscience, Geriatrics and Gerontology, Clinical Neurology
Language:English
Date:1 April 2019
Deposited On:15 Mar 2019 12:44
Last Modified:15 Mar 2020 01:00
Publisher:Elsevier
ISSN:0197-4580
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.neurobiolaging.2019.01.003
PubMed ID:30743056
Project Information:
  • : FunderFP7
  • : Grant ID250356
  • : Project TitlePRIONS - The prion protein in health and disease
  • : FunderSNSF
  • : Grant ID310030B_160329
  • : Project TitleThe prion protein in health and disease
  • : FunderSNSF
  • : Grant IDCRSII3_147660
  • : Project TitleCalcium imaging of cellular and circuit dysfunctions in neurodegeneration
  • : FunderCRPP
  • : Grant ID
  • : Project TitleSmall RNAS
  • : FunderCRPP
  • : Grant ID
  • : Project TitleHHLD
  • : FunderSystemsX.ch
  • : Grant ID
  • : Project TitleSystems Biology of Prion Diseases
  • : FunderSystemsX.ch
  • : Grant ID
  • : Project TitleSynucleiX
  • : FunderFP7
  • : Grant ID278611
  • : Project TitleNOX enzymes as mediators of inflammation-triggered neurodegeneration: modulating NOX enzymes as novel therapies
  • : FunderFP7
  • : Grant ID222887
  • : Project TitleProtecting the food chain from prions: shaping European priorities through basic and applied research

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