Figure 3.

Suggested mode of action of an anti-prionic compound (from right to left): The desired anti-prionic compound should preferentially bind Aβ monomers and stabilize them in their native, intrinsically disordered conformation. This can be envisioned in a transient manner and is not necessarily in a 1:1 stoichiometry. When the compound is approaching the prion assembly, it will interact with one of the Aβ monomer subunits and thereby pushing its conformation towards the native one that does not perfectly fit to the rest of the prion particle. Thus, the prion particle is already destabilized a bit by this interaction. Each additional anti-prionic drug molecule will interact with further Aβ monomer subunits, further destabilizing and ultimately destroying and fully disassembling the Aβ prion particle. From a physicochemical and biophysical perspective, one would expect the action to be highly cooperative, clearly sub-stoichiometric (relative to the number of Aβ monomer subunits) and possibly even catalytic, because the drug molecules are not consumed during the prion destruction.