The role of macrophage scavenger receptor 1 (Msr1) in prion pathogenesis
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Abstract
The progression of prion diseases is accompanied by the accumulation of prions in the brain. Ablation of microglia enhances prion accumulation and accelerates disease progression, suggesting that microglia play a neuroprotective role by clearing prions. However, the mechanisms underlying the phagocytosis and clearance of prion are largely unknown. The macrophage scavenger receptor 1 (Msr1) is an important phagocytic receptor expressed by microglia in the brain and is involved in the uptake and clearance of soluble amyloid-β. We therefore asked whether Msr1 might play a role in prion clearance and assessed the scavenger function of Msr1 in prion pathogenesis. We found that Msr1 expression was upregulated in prion-infected mouse brains. However, Msr1 deficiency did not change prion disease progression or lesion patterns. Prion deposition in Msr1 deficient mice was similar to their wild-type littermates. In addition, prion-induced neuroinflammation was not affected by Msr1 ablation. We conclude that Msr1 does not play a major role in prion pathogenesis. Key messages: Msr1 expression is upregulated in prion-infected mouse brains at the terminal stage Msr1 deficiency does not affect prion disease progression Msr1 does not play a major role in prion clearance or prion pathogenesis Microglia-mediated phagocytosis and clearance of Aβ and prion may adopt distinct molecular pathways
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Neither the 'eat me'-protein developmental endothelial locus-1 nor the 'don't eat me'-receptor signal regulatory protein SIRPa, nor the macrophage scavenger receptor 1 (Msr1) influence the prion disease course, since their depletion had no effect on disease pathophysiology.
“However, neither the “eat me”-protein developmental endothelial locus-1 nor the “don’t eat me”-receptor signal regulatory protein SIRPa, nor the macrophage scavenger receptor 1 (Msr1) influence the prion disease course, since their depletion had no effect on disease pathophysiology [85,86,87].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [87]
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Loss of Homeostatic Microglia Signature in Prion Diseases
Wang, Y., Hartmann, K., Thies, E., Mohammadi, B., Altmeppen, H., Sepulveda-Falla, D., Glatzel, M., & Krasemann, S. (2022) · Cells · doi:10.3390/cells11192948 · Cited by 12 · see citing works
- Authors
- Li, B., Chen, M., Aguzzi, A., & Zhu, C.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- University Hospital Zurich (CH)
- Fudan University (CN)
- Corresponding author
- Aguzzi, Adriano
- Zhu, Caihong
- Venue
- Journal of Molecular Medicine
- Published
- 2021-03-23
- Volume
- 99
- Issue
- 6
- Pages
- 877-887
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- PMC
- PMC8164582
- OpenAlex
- W3136377073
- Cited by
- 7
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Molecular Medicine (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- European Research Council (670958)
- European Union
- Swiss National Foundation
- SystemsX.ch
- Klinische Forschungsschwerpunkte
- National Natural Science Foundation of China (82071436)
- Shanghai Pujiang Program (20PJ1401100)
- Research Startup Funds of Fudan University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- MSR1, prion disease, prion clearance, microglia, phagocytosis, prion accumulation, neuroinflammation, prion pathogenesis, amyloid-beta clearance
- MeSH terms
- Animals, Brain, Disease Models, Animal, Disease Susceptibility, Immunohistochemistry, Phagocytosis, Biomarkers, Gene Expression, Prion Diseases, Mice, Knockout, Disease Progression, PrPSc Proteins, Scavenger Receptors, Class A, Mice
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