Department of Medicine, Division of Infectious Diseases and Immunology
Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Immunology and Infectious Disease | Molecular and Cellular Neuroscience | Nervous System Diseases | Psychiatry and Psychology
Alzheimer's disease is the world's most common neurodegenerative disorder. It is associated with neuroinflammation involving activation of microglia by beta-amyloid (Abeta) deposits. Based on previous studies showing apoptosis-associated speck-like protein containing a CARD (ASC) binding and cross-seeding extracellular Abeta, we investigate the propagation of ASC between primary microglia and the effects of ASC-Abeta composites on microglial inflammasomes and function. Indeed, ASC released by a pyroptotic cell can be functionally built into the neighboring microglia NOD-like receptor protein (NLRP3) inflammasome. Compared with protein-only application, exposure to ASC-Abeta composites amplifies the proinflammatory response, resulting in pyroptotic cell death, setting free functional ASC and inducing a feedforward stimulating vicious cycle. Clustering around ASC fibrils also compromises clearance of Abeta by microglia. Together, these data enable a closer look at the turning point from acute to chronic Abeta-related neuroinflammation through formation of ASC-Abeta composites.
ASC, Alzheimer’s disease, Aβ, NLRP3 inflammasome, microglia
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Copyright 2020 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DOI of Published Version
Friker LL, Scheiblich H, Hochheiser IV, Brinkschulte R, Riedel D, Latz E, Geyer M, Heneka MT. β-Amyloid Clustering around ASC Fibrils Boosts Its Toxicity in Microglia. Cell Rep. 2020 Mar 17;30(11):3743-3754.e6. doi: 10.1016/j.celrep.2020.02.025. PMID: 32187546. Link to article on publisher's site
Friker LL, Scheiblich H, Hochheiser IV, Brinkschulte R, Riedel D, Latz E, Geyer M, Heneka MT. (2020). beta-Amyloid Clustering around ASC Fibrils Boosts Its Toxicity in Microglia. Open Access Articles. https://doi.org/10.1016/j.celrep.2020.02.025. Retrieved from https://escholarship.umassmed.edu/oapubs/4180
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