Induction of protein aggregation in zebrafish embryos as a method for the screening of new drugs or mutations against proteinopathies.

The sustained increase in the prevalence of protein aggregation related diseases requires the development of feasible methods for the design of therapeutic alternatives. The procedure traditionally used for the search of drugs or therapeutic mutations includes experiments, designed to prevent the aggregation of model proteins, which are then complemented with cellular toxicity studies , slowing down the finding of solutions. To address this, we have developed a protocol that facilitates the search of molecules and anti-aggregation mutations since it allows to evaluate their therapeutic capabilities directly in experiments with the use of zebrafish early embryos.

The chaperonin CCT promotes the formation of fibrillar aggregates of γ-tubulin.

The type II chaperonin CCT is involved in the prevention of the pathogenesis of numerous human misfolding disorders, as it sequesters misfolded proteins, blocks their aggregation and helps them to achieve their native state. In addition, it has been reported that CCT can prevent the toxicity of non-client amyloidogenic proteins by the induction of non-toxic aggregates, leading to new insight in chaperonin function as an aggregate remodeling factor. Here we add experimental evidence to this alternative mechanism by which CCT actively promotes the formation of conformationally different aggregates of γ-tubulin, a non-amyloidogenic CCT client protein, which are mediated by specific CCT-γ-tubulin interactions.

Identification of Key Amino Acid Residues Modulating Intracellular and In vitro Microcin E492 Amyloid Formation.

Microcin E492 (MccE492) is a pore-forming bacteriocin produced and exported by Klebsiella pneumoniae RYC492. Besides its antibacterial activity, excreted MccE492 can form amyloid fibrils in vivo as well as in vitro. It has been proposed that bacterial amyloids can be functional playing a biological role, and in the particular case of MccE492 it would control the antibacterial activity.