%0 Journal Article
%A Friker, Lea L.
%A Scheiblich, Hannah
%A Hochheiser, Inga V.
%A Brinkschulte, Rebecca
%A Riedel, Dietmar
%A Latz, Eicke
%A Geyer, Matthias
%A Heneka, Michael T.
%T β-Amyloid Clustering around ASC Fibrils Boosts Its Toxicity in Microglia
%J Cell reports
%V 30
%N 11
%@ 2211-1247
%C [New York, NY]
%I Elsevier
%M DZNE-2020-01240
%P 3743 - 3754.e6
%D 2020
%X Alzheimer’s disease is the world’s most common neurodegenerative disorder. It is associated with neuroinflammation involving activation of microglia by β-amyloid (Aβ) deposits. Based on previous studies showing apoptosis-associated speck-like protein containing a CARD (ASC) binding and cross-seeding extracellular Aβ, we investigate the propagation of ASC between primary microglia and the effects of ASC-Aβ 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-Aβ 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 Aβ by microglia. Together, these data enable a closer look at the turning point from acute to chronic Aβ-related neuroinflammation through formation of ASC-Aβ composites.
%K Amyloid beta-Peptides: metabolism
%K Amyloid beta-Peptides: toxicity
%K Amyloid beta-Peptides: ultrastructure
%K Animals
%K CARD Signaling Adaptor Proteins: metabolism
%K Caspase 1: metabolism
%K Cells, Cultured
%K Humans
%K Inflammasomes: metabolism
%K Interleukin-1beta: metabolism
%K Mice, Inbred C57BL
%K Microglia: drug effects
%K Microglia: metabolism
%K Microglia: pathology
%K Models, Biological
%K NLR Family, Pyrin Domain-Containing 3 Protein: metabolism
%K Proteolysis: drug effects
%K Pyroptosis: drug effects
%K Signal Transduction: drug effects
%K Toll-Like Receptor 2: metabolism
%K Toll-Like Receptor 4: metabolism
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC8729885
%$ pmid:32187546
%R 10.1016/j.celrep.2020.02.025
%U https://pub.dzne.de/record/151661