A.A. Ustyugov, N.N. Ninkina

One of the promising approaches in preventing and correcting many common human neurodegenerative diseases lies in the development of drugs that potentially prevent the formation of aggregates of pathogenic forms of proteins and/or activate intracellular defense systems that control degradation of protein aggregation products. The use of transgenic animals provides optimizes the design and study of disease-modifying neuroprotective drugs. We have developed a model of progressive in vivo proteinopathy in genetically modified mice that is induced by the increased expression of amyloidogenic protein gamma-synuclein. In our model mice we see developing of proteinopathy that processed with age and accompanied by the accumulation of histopathological inclusions in the tissues of the nervous system of transgenic animals that are mainly composed of aggregated gamma-synuclein. As a result of the detailed description of this line it is possible use gamma-synuclein transgenic animals as a selection tool for the next-generation drugs that act directly on the molecular pathogenesis of key aspects of proteinopathy. The appearing genetic models of neurodegenerative diseases can significantly optimize the development, testing and selection of new drugs that particularly target the pathogenesis of the diseases. Our newly developed genetic model of progressive proteinopathy provides a convenient system that reproduces the key stages of the aggregation of conformationally unstable proteins and the formation of amyloid-like inclusions in the nervous system of animals. These pathogenic components of proteinopathy are currently considered as potential targets for therapeutic intervention and for the discovery of innovative disease-modifying drugs