An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils.

摘要: Removing or preventing the formation of [Formula: see text]-synuclein aggregates is a plausible strategy against Parkinson's disease. To this end, we have engineered text]-wrapin AS69 to bind monomeric with high affinity. In cultured cells, reduced self-interaction and visible aggregates. flies, locomotor deficit resulting from expression in neuronal cells. biophysical experiments vitro, highly sub-stoichiometrically inhibited both primary autocatalytic secondary nucleation processes, even presence large excess monomer. We present evidence that AS69-[Formula: complex, rather than free AS69, inhibitory species responsible for sub-stoichiometric inhibition nucleation. These results represent new paradigm affinity monomer binders can lead strongly processes.