Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer’s Disease

Figure 2

Modulation of tau aggregation by metal ions. Hyperphosphorylated (P) tau undergoes aggregation, which is influenced by metal ion binding. Tau phosphorylation facilitates Fe³⁺ binding that promotes the formation of paired helical filaments (PHF) and further tau fibrillation. The reduction of Fe³⁺ to Fe²⁺ reverts PHF formation. Zn²⁺ binding at high ratios promotes the formation of amorphous tau oligomers, whereas, at low ratios, PHF are formed. Both Ca²⁺ and Mg²⁺ binding to PHF favour the conversion into amorphous off-pathway aggregates. A neurofibrillary tangle is depicted in a representation at the bottom left corner of the figure. See text for details. Adapted from [30].