The coordination chemistry of aluminium in neurodegenerative disease

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.

► 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.
► 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.