VACCINE

Coordination Chemistry Reviews • October 2012
Metal Ions in Neurodegenerative Diseases
The coordination chemistry of aluminium
in neurodegenerative disease
by Christopher Exley
Abstract
The coordination chemistry of a metal ion defines its optimal association
with a biomolecule such that its binding by specific ligands on that molecule
confers function and biological purpose. Aluminium is a non-essential
metal with no known biological role which means that its coordination
neurochemistry defines aluminium’s putative role in a number of
neurodegenerative diseases. In examining this chemistry it is found that
very little is known about the complexes formed and ligands involved in
aluminium’s interactions with neurochemically-relevant ligands. Aluminium’s
action as a pro-oxidant as well as an excitotoxin are highlighted
while the evidence for its interactions with amyloid beta, tau and DNA are
discussed and it is concluded that it is too early to discount these ligands
as targets for the neurotoxicity of aluminium.
Highlights
• There are few quantitaive data describing the coordination chemistry of
aluminium in neurodegenerative disease.
• One compelling line of evidence relates to the putative aluminium superoxide
semi-reduced radical ion AlO22+ and its powerful action as a
pro-oxidant.
• Another important candidate is aluminium’s complex with ATP and its
potential to disrupt neuronal signalling and induce excitotoxicity.
“In examining this chemistry it is found that
very little is known about the complexes formed
and ligands involved in aluminium’s interactions
with neurochemically-relevant ligands. Aluminium’s
action as a pro-oxidant as well as an excitotoxin are
highlighted while the evidence for its interactions with
amyloid beta, tau and DNA are discussed and it is
concluded that it is too early to discount these ligands
as targets for the neurotoxicity of aluminium.”
• Though there are no quantitative data to describe aluminium’s interactions
with amyloid beta this does not preclude their association in the
brain.
• The biological reactivity of aluminium supports myriad as yet unidentified
interactions with biomolecules associated with brain function in
health and disease.
http://www.sciencedirect.com/science/article/pii/S0010854512000392