TY - JOUR
T1 - RAGE and amyloid beta interactions
T2 - Atomic force microscopy and molecular modeling
AU - Chaney, Michael O.
AU - Stine, W. Blaine
AU - Kokjohn, Tyler A.
AU - Kuo, Yu Min
AU - Esh, Chera
AU - Rahman, Afroza
AU - Luehrs, Dean C.
AU - Schmidt, Ann Marie
AU - Stern, David
AU - Yan, Shi Du
AU - Roher, Alex E.
N1 - Funding Information:
This work was supported by the NIA Grants: AG-19795 and P01 AG-17490 and by the State of Arizona Alzheimer's Disease Research Center.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/6/30
Y1 - 2005/6/30
N2 - In the AD brain, there are elevated amounts of soluble and insoluble Aβ peptides which enhance the expression of membrane bound and soluble receptor for advanced glycation end products (RAGE). The binding of soluble Aβ to soluble RAGE inhibits further aggregation of Aβ peptides, while membrane bound RAGE-Aβ interactions elicit activation of the NF-κB transcription factor promoting sustained chronic neuroinflammation. Atomic force microscopy observations demonstrated that the N-terminal domain of RAGE, by interacting with Aβ, is a powerful inhibitor of Aβ polymerization even at prolonged periods of incubation. Hence, the potential RAGE-Aβ structural interactions were further explored utilizing a series of computational chemistry algorithms. Our modeling suggests that a soluble dimeric RAGE assembly creates a positively charged well into which the negative charges of the N-terminal domain of dimeric Aβ dock.
AB - In the AD brain, there are elevated amounts of soluble and insoluble Aβ peptides which enhance the expression of membrane bound and soluble receptor for advanced glycation end products (RAGE). The binding of soluble Aβ to soluble RAGE inhibits further aggregation of Aβ peptides, while membrane bound RAGE-Aβ interactions elicit activation of the NF-κB transcription factor promoting sustained chronic neuroinflammation. Atomic force microscopy observations demonstrated that the N-terminal domain of RAGE, by interacting with Aβ, is a powerful inhibitor of Aβ polymerization even at prolonged periods of incubation. Hence, the potential RAGE-Aβ structural interactions were further explored utilizing a series of computational chemistry algorithms. Our modeling suggests that a soluble dimeric RAGE assembly creates a positively charged well into which the negative charges of the N-terminal domain of dimeric Aβ dock.
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U2 - 10.1016/j.bbadis.2005.03.014
DO - 10.1016/j.bbadis.2005.03.014
M3 - Article
C2 - 15882940
AN - SCOPUS:20444462454
VL - 1741
SP - 199
EP - 205
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 1-2
ER -