Amyloid Fibril Formation of α-Synuclein Is Accelerated by Preformed Amyloid Seeds of Other Proteins

Abstract

Synuclein is one of the causative proteins of familial Parkinson disease, which is characterized by neuronal inclusions named Lewy bodies. Lewy bodies include not only-synuclein but also aggregates of other proteins. This fact raises a question as to whether the formation of-synuclein amyloid fibrils in Lewy bodies may occur via interaction with fibrils derived from different proteins. To probe this hypothesis, we investigated in vitro fibril formation of human-synuclein in the presence of preformed fibril seeds of various different proteins. We used three proteins, Escherichia coli chapero-nin GroES, hen lysozyme, and bovine insulin, all of which have been shown to form amyloid fibrils. Very surprisingly, the formation of-synuclein amyloid fibril was accelerated markedly in the presence of preformed seeds of GroES, lysozyme, and insulin fibrils. The structural characteristics of the natively unfolded state of-synuclein may allow binding to various protein particles, which in turn triggers the formation (extension) of-synuclein amyloid fibrils. This finding is very important for understanding the molecular mechanism of Parkinson disease and also provides interesting implications into the mechanism of transmissible conformational diseases.