Neglected N-Truncated Amyloid-β Peptide and Its Mixed Cu-Zn Complexes

Amyloid-β (Aβ) peptides are involved in Alzheimer's disease (AD) development. The interactions of these peptides with copper and zinc ions also seem to be crucial for this pathology. Although Cu(II) and Zn(II) ions binding by Aβ peptides has been scrupulously investigated, surprisingly, this phenomenon has not been so thoroughly elucidated for N-truncated Aβ_4-x-probably the most common version of this biomolecule. This negligence also applies to mixed Cu-Zn complexes. From the structural in silico analysis presented in this work, it appears that there are two possible mixed Cu-Zn(Aβ_4-x) complexes with different stoichiometries and, consequently, distinct properties. The Cu-Zn(Aβ_4-x) complex with 1:1:1 stoichiometry may have a neuroprotective superoxide dismutase-like activity. On the other hand, another mixed 2:1:2 Cu-Zn(Aβ_4-x) complex is perhaps a seed for toxic oligomers. Hence, this work proposes a novel research direction for our better understanding of AD development.