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Identification of molecular compounds critical to Alzheimer's‐like plaque formation
Author(s) -
Gellermann Gerald P.,
Ullrich Kathrin,
Unger Christiane,
Fändrich Marcus,
Sauter Simon,
Diekmann Stephan
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21311
Subject(s) - amyloid (mycology) , chemistry , senile plaques , fibril , p3 peptide , biochemistry of alzheimer's disease , extracellular , alzheimer's disease , microbiology and biotechnology , in vivo , biophysics , biochemistry , amyloid precursor protein , biology , pathology , disease , medicine , inorganic chemistry
Amyloid diseases are characterized by the formation of insoluble amyloid fibrils from previously soluble polypeptides. In Alzheimer's disease (AD), amyloid fibrils, formed from β‐amyloid peptides, are deposited as extracellular amyloid plaques only inside the brain. As previously shown, Alzheimer's‐like plaque formation in human monocyte culture recapitulates the features of in vivo amyloid plaque formation. Here we show that this cell model can be used to screen compounds that potentially influence amyloid formation in a throughput manner. We found that cellular amyloid fibril formation can be enhanced by dextran sulfate as well as heparin and can be impaired by stabilization of a micell‐like β‐amyloid conformer by using myoinositol or by inhibition of phagocytosis with cytochalasin D. Altogether, our data demonstrate the utility of this cell model for investigating pathways and molecular interactions critical to amyloidogenesis. © 2007 Wiley‐Liss, Inc.