Journal Article

DZNE-2020-01240

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png β-Amyloid Clustering around ASC Fibrils Boosts Its Toxicity in Microglia

Friker, L. L. ; Scheiblich, H. ; Hochheiser, I. V. ; Brinkschulte, R. ; Riedel, D. ; Latz, E. ; Geyer, M. ; Heneka, M. T. (Last author)DZNE*

2020
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2020.02.025

Abstract: 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.

Keyword(s): Amyloid beta-Peptides: metabolism (MeSH) ; Amyloid beta-Peptides: toxicity (MeSH) ; Amyloid beta-Peptides: ultrastructure (MeSH) ; Animals (MeSH) ; CARD Signaling Adaptor Proteins: metabolism (MeSH) ; Caspase 1: metabolism (MeSH) ; Cells, Cultured (MeSH) ; Humans (MeSH) ; Inflammasomes: metabolism (MeSH) ; Interleukin-1beta: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Microglia: drug effects (MeSH) ; Microglia: metabolism (MeSH) ; Microglia: pathology (MeSH) ; Models, Biological (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: metabolism (MeSH) ; Proteolysis: drug effects (MeSH) ; Pyroptosis: drug effects (MeSH) ; Signal Transduction: drug effects (MeSH) ; Toll-Like Receptor 2: metabolism (MeSH) ; Toll-Like Receptor 4: metabolism (MeSH)

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Contributing Institute(s):

1. Neuroinflammation, Biomarker (AG Heneka ; AG Heneka)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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