ArticleFrontiers in immunology2022
Brain Cells Release Calreticulin That Attracts and Activates Microglia, and Inhibits Amyloid Beta Aggregation and Neurotoxicity.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Synthetic viral RNA mimetics induce neuronal loss through microglial phagocytosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Gene Expression Analysis of Mitochondria-Associated Membrane (MAM)-Related Genes in ER Stress and Alzheimer's Disease.Cellular and molecular neurobiology · 2026Article
- The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease.Cell death & disease · 2026Article
- Characterization and biological health implications of microRNAs from human milk and infant formulas.NPJ science of food · 2025Review
- Contemporary insights into neuroimmune interactions across development and aging.Frontiers in neurology · 2025Review
- New preclinical biomarkers for prion diseases in the cerebrospinal fluid proteome revealed by mass spectrometry.The veterinary quarterly · 2024Article
- Permethrin exposure primes neuroinflammatory stress response to drive depression-like behavior through microglial activation in a mouse model of Gulf War Illness.Journal of neuroinflammation · 2024Article
- Optical biosensor based on weak measurement for ultra-sensitive detection of calreticulin in human serum.Biomedical optics express · 2024Article
- Article
- Review
- Intracellular DAMPs in Neurodegeneration and Their Role in Clinical Therapeutics.Molecular neurobiology · 2023Review
- The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery.Biomolecules · 2023Review
- LRPAP1 is released from activated microglia and inhibits microglial phagocytosis and amyloid beta aggregation.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Calreticulin is a chaperone, normally found in the endoplasmic reticulum, but can be released by macrophages into the extracellular medium. It is also found in cerebrospinal fluid bound to amyloid beta (Aβ). We investigated whether brain cells release calreticulin, and whether extracellular calreticulin had any effects on microglia and neurons relevant to neuroinflammation and neurodegeneration. We found that microglia release nanomolar levels of calreticulin when inflammatory-activated with lipopolysaccharide, when endoplasmic reticulum stress was induced by tunicamycin, or when cell death was induced by staurosporine, and that neurons release calreticulin when crushed. Addition of nanomolar levels of extracellular calreticulin was found to chemoattract microglia, and activate microglia to release cytokines TNF-α, IL-6 and IL-1β, as well as chemokine (C-C motif) ligand 2. Calreticulin blocked Aβ fibrillization and modified Aβ oligomerization, as measured by thioflavin T fluorescence and transmission electron microscopy. Extracellular calreticulin also altered microglial morphology and proliferation, and prevented Aβ-induced neuronal loss in primary neuron-glial cultures. Thus, calreticulin is released by microglia and neurons, and acts: as an alarmin to recruit and activate microglia, as an extracellular chaperone to prevent Aβ aggregation, and as a neuroprotectant against Aβ neurotoxicity.
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Registered trials
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