In this section
@article{Branch:2017:10.1021/acschemneuro.7b00121,
author = {Branch, T and Barahona, M and Dodson, C and Ying, L},
doi = {10.1021/acschemneuro.7b00121},
journal = {ACS Chemical Neuroscience},
pages = {1970--1979},
title = {Kinetic analysis reveals the identity of Aβ-metal complex responsible for the initial aggregation of Aβ in the synapse},
url = {http://dx.doi.org/10.1021/acschemneuro.7b00121},
volume = {8},
year = {2017}
}
TY - JOUR
AB - The mechanism of Aβ aggregation in the absence of metal ions is well established, yet the role that Zn2+ and Cu2+, the two most studied metal ions, released during neurotransmission, paly in promoting Aβ aggregation in the vicinity of neuronal synapses remains elusive. Here we report the kinetics of Zn2+ binding to Aβ and Zn2+/Cu2+ binding to Aβ-Cu to form ternary complexes under near physiological conditions (nM Aβ, μM metal ions). We find that these reactions are several orders of magnitude slower than Cu2+ binding to Aβ. Coupled reaction-diffusion simulations of the interactions of synaptically released metal ions with Aβ show that up to a third of Aβ is Cu2+-bound under repetitive metal ion release, while any other Aβ-metal complexes (including Aβ-Zn) are insignificant. We therefore conclude that Zn2+ is unlikely to play an important role in the very early stages (i.e., dimer formation) of Aβ aggregation, contrary to a widely held view in the subject. We propose that targeting the specific interactions between Cu2+ and Aβ may be a viable option in drug development efforts for early stages of AD.
AU - Branch,T
AU - Barahona,M
AU - Dodson,C
AU - Ying,L
DO - 10.1021/acschemneuro.7b00121
EP - 1979
PY - 2017///
SN - 1948-7193
SP - 1970
TI - Kinetic analysis reveals the identity of Aβ-metal complex responsible for the initial aggregation of Aβ in the synapse
T2 - ACS Chemical Neuroscience
UR - http://dx.doi.org/10.1021/acschemneuro.7b00121
UR - http://hdl.handle.net/10044/1/49341
VL - 8
ER -
