In vitro Modeling of Prion Strain Tropism

Abstract

Prions are atypical infectious agents lacking genetic material. Yet, various strains have been isolated from animals and humans using experimental models. They are distinguished by the resulting pattern of disease, including the localization of PrPsc deposits and the spongiform changes they induce in the brain of affected individuals. In this paper, we discuss the emerging use of cellular and acellular models to decipher the mechanisms involved in the strain-specific targeting of distinct brain regions. Recent studies suggest that neuronal cultures, protein misfolding cyclic amplification, and combination of both approaches may be useful to explore this under-investigated but central domain of the prion field.

Automated microscopic measurement of fibrinaloid microclots and their degradation by nattokinase, the main natto protease

“…[108,109]), the existence of these 'fibrinaloid' microclots implies their comparative resistance to normal fibrinolysis [110,111], with their precise structures [112] being affected by other small and macromolecules and ions that they may have bound [97,103,[113][114][115][116][117][118][119]. The varieties of stable macrostates into which a given amyloidogenic sequence can fold (even under the same conditions [120,121]) are referred to as different 'strains' [122][123][124][125][126][127][128][129][130][131][132] or 'polymorphisms' [133][134][135][136][137][138][139][140][141][142][143][144], and in some cases are sufficiently stable (i.e. kinetically isolated from other macrostates) that they are even heritable [122,[145][146][147][148][149][150][151]…”