期刊
CELL REPORTS
卷 30, 期 11, 页码 3743-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.02.025
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资金
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy [EXC2151 -390873048]
- NIH [R01 AG059752-02]
Alzheimer's disease is the world's most common neurodegenerative disorder. It is associated with neuroinflammation involving activation of microglia by beta-amyloid (A beta) deposits. Based on previous studies showing apoptosis-associated speck-like protein containing a CARD (ASC) binding and cross-seeding extracellular A beta, we investigate the propagation of ASC between primary microglia and the effects of ASC-A beta 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 proteinonly application, exposure to ASC-A beta 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 A beta by microglia. Together, these data enable a closer look at the turning point from acute to chronic A beta-related neuroinflammation through formation of ASC-A beta composites.
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