Synthetic Sulfated Polymers Control Amyloid Aggregation of Ovine Prion Protein and Decrease Its Toxicity.

Amyloid aggregation, including aggregation and propagation of prion protein, is a key factor in numerous human diseases, so-called amyloidosis, with a very poor ability for treatment or prevention. The present work describes the effect of sulfated or sulfonated polymers (sodium dextran sulfate, polystyrene sulfonate, polyanethole sulfonate, and polyvinyl sulfate) on different stages of amyloidogenic conversion and aggregation of the prion protein, which is associated with prionopathies in humans and animals. All tested polymers turned out to induce amyloid conversion of the ovine prion protein.

Tightly bound polyelectrolytes enhance enzyme proteolysis and destroy amyloid aggregates.

The use of polyelectrolytes is a prospective approach to form nanocomplexes to transport different compounds including proteins. In many cases, the bound protein should be digested after delivery to the target. In the present work, we studied proteolysis of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the complexes with polyelectrolytes.

Properties of substances inhibiting aggregation of oxidized GAPDH: Data on the interaction with the enzyme and the impact on its intracellular content.

This data is related to our paper "Small molecules preventing GAPDH aggregation are therapeutically applicable in cell and rat models of oxidative stress" (Lazarev et al. [1]) where we explore therapeutic properties of small molecules preventing GAPDH aggregation in cell and rat models of oxidative stress. The present article demonstrates a few of additional properties of the chemicals shown to block GAPDH aggregation such as calculated site for targeting the enzyme, effects on GAPDH glycolytic activity, influence on GAPDH intracellular level and anti-aggregate activity of pure polyglutamine exemplifying a denatured protein.

Small molecules preventing GAPDH aggregation are therapeutically applicable in cell and rat models of oxidative stress.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the most abundant targets of the oxidative stress. Oxidation of the enzyme causes its inactivation and the formation of intermolecular disulfide bonds, and leads to the accumulation of GAPDH aggregates and ultimately to cell death. The aim of this work was to reveal the ability of chemicals to break the described above pathologic linkage by inhibiting GAPDH aggregation.