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Amyloid β: one of three danger‐associated molecules that are secondary inducers of the proinflammatory cytokines that mediate A lzheimer's disease
Author(s) -
Clark I A,
Vissel B
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13181
Subject(s) - proinflammatory cytokine , inflammation , cytokine , immunology , receptor , genetically modified mouse , microbiology and biotechnology , amyloid (mycology) , biology , transgene , chemistry , biochemistry , gene , botany
This review concerns how the primary inflammation preceding the generation of certain key damage‐associated molecular patterns ( DAMPs ) arises in A lzheimer's disease ( AD ). In doing so, it places soluble amyloid β (Aβ), a protein hitherto considered as a primary initiator of AD, in a novel perspective. We note here that increased soluble Aβ is one of the proinflammatory cytokine‐induced DAMPs recognized by at least one of the toll‐like receptors on and in various cell types. Moreover, Aβ is best regarded as belonging to a class of DAMPs , as do the S100 proteins and HMBG 1, that further exacerbate production of these same proinflammatory cytokines, which are already enhanced, and induces them further. Moreover, variation in levels of other DAMPs of this same class in AD may explain why normal elderly patients can exhibit high Aβ plaque levels, and why removing Aβ or its plaque does not retard disease progression. It may also explain why mouse transgenic models, having been designed to generate high Aβ, can be treated successfully by this approach.