TY  - JOUR
AU  - Donner, Lili
AU  - Gremer, Lothar
AU  - Ziehm, Tamar
AU  - Gertzen, Christoph G. W.
AU  - Gohlke, Holger
AU  - Willbold, Dieter
AU  - Elvers, Margitta
TI  - Relevance of N-terminal residues for amyloid-β binding to platelet integrin α IIb β 3 , integrin outside-in signaling and amyloid-β fibril formation
JO  - Cellular signalling
VL  - 50
SN  - 0898-6568
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - FZJ-2018-04075
SP  - 121 - 130
PY  - 2018
AB  - A pathological hallmark of Alzheimer's disease (AD) is the aggregation of amyloid-β peptides (Aβ) into fibrils, leading to deposits in cerebral parenchyma and vessels known as cerebral amyloid angiopathy (CAA). Platelets are major players of hemostasis but are also implicated in AD. Recently we provided strong evidence for a direct contribution of platelets to AD pathology. We found that monomeric Aβ40 binds through its RHDS sequence to integrin αIIbβ3, and promotes the formation of fibrillar Aβ aggregates by the secretion of adenosine diphosphate (ADP) and the chaperone protein clusterin (CLU) from platelets. Here we investigated the molecular mechanisms of Aβ binding to integrin αIIbβ3 by using Aβ11 and Aβ16 peptides. These peptides include the RHDS binding motif important for integrin binding but lack the central hydrophobic core and the C-terminal sequence of Aβ. We observed platelet adhesion to truncated N-terminal Aβ11 and Aβ16 peptides that was not mediated by integrin αIIbβ3. Thus, no integrin outside-in signaling and reduced CLU release was detected. Accordingly, platelet mediated Aβ fibril formation was not observed. Taken together, the RHDS motif of Aβ is not sufficient for Aβ binding to platelet integrin αIIbβ3 and platelet mediated Aβ fibril formation but requires other recognition or binding motifs important for platelet mediated processes in CAA. Thus, increased understanding of the molecular mechanisms of Aβ binding to platelet integrin αIIbβ3 is important to understand the role of platelets in amyloid pathology.
LB  - PUB:(DE-HGF)16
C6  - pmid:29964150
UR  - <Go to ISI:>//WOS:000441493100012
DO  - DOI:10.1016/j.cellsig.2018.06.015
UR  - https://juser.fz-juelich.de/record/849980
ER  -