Yong Zhang's research while affiliated with Central China Normal University and other places

To study the effect of Cu2+ and Zn2+ on amyloid-beta peptides (Abeta) aggregation, the morphology, size and cell toxicity of Abeta40 aggregates formed with the metal ions have been observed by the methods including ultraviolet spectroscopy, fluorescence spectroscopy and transmission electron microscopy. The results showed that Cu2+ and Zn2+ can accelerate Abeta40 aggregation, and both changed the morphology and size of Abeta40 aggregates. Zn2+ induced Abeta40 to form fibrous Abeta40 aggregates, while the amorphous and fibrous aggregates were produced by the interaction between Cu2+ and Abeta40. In addition, H2O2 was produced when Abeta40 reduced Cu2+. The relationship between metal ions and Abeta40 aggregates was analyzed, and the function of metal ions in Alzheimer's disease (AD) was illustrated in the research.

Amyloid proteins, mainly including amyloid-β peptides, prion proteins, α-synuclein, copper/zinc superoxide dismutase, as well as the bacterial protein RepA, are characterized by the deposition in a variety of tissues or cells as aggregated species (amyloids or insoluble deposits or inclusions) that share a distinctive β-sheet-rich fibrillar ultrastructure. Although the amyloid is predominantly proteinaceous, careful examination of disease tissues and cells has revealed the presence of a significant quantity of polyanionic species including nucleic acids and polysaccharides associated with the amyloid. For example, in the brain tissues from victims of Alzheimer's disease, nucleic acids have been detected in neurofibrillary tangles and intracellular inclusions primarily composed of the tau protein, as well as in senile plaques composed of the amyloid-β peptides. Therefore, much effort has been directed to understanding the roles of the ubiquitous polyanionic species such as nucleic acids in the aggregation of amyloid proteins. Increasing evidence indicates that the amyloid proteins exhibit a high binding affinity for nucleic acids and the binding is mainly driven by electrostatic interactions between both. The association with nucleic acids leads to significant variations of the amyloid proteins in conformation. The nucleic acids have been observed to be capable of significantly inducing and accelerating the aggregation of amyloid proteins likely through a template effect. The template effect could restrict the orientations of amyloid proteins along nucleic acid strands and increase the local concentrations of amyloid proteins on nucleic acid surfaces, leading to enhancement in the intermolecular hydrophobic contacts of amyloid proteins. The nucleic acids have also been found to occur as an intrinsic or transient component in the resulted proteinaceous aggregates.

The fluorescent chelator (FC-1) was designed by combining a metal-chelating unit and a ThT-based Aβ aggregate-binding fluorescent unit. FC-1 is a cell membrane-penetrable chelator with a moderate chelation ability to Cu(2+) and Zn(2+) and can target metal-Aβ40 aggregates. Treatment with FC-1 led to enhanced cytotoxicity of the aggregates, because the aggregates were converted into a pool of oligomers.