C-terminal truncation of α-synuclein promotes amyloid fibril amplification at physiological pH.

ABSTRACT: Parkinson's disease is one of the major neurodegenerative disorders affecting the ageing populations of the modern world. One of the hallmarks of this disease is the deposition of aggregates, mainly of the small pre-synaptic protein α-synuclein (AS), in the brains of patients. Several very significantly modified forms of AS have been found in these deposits including those resulting from truncations of the protein at its C-terminus. Here, we report how two physiologically relevant C-terminal truncations of AS, AS(1-119) and AS(1-103), where either half or virtually all of the C-terminal domain, respectively, has been truncated, affect the mechanism of AS aggregation and the properties of the fibrils formed. In particular, we have found that the deletion of these C-terminal residues induces

SUBMITTER: van der Wateren IM 

PROVIDER: S-EPMC6048717 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature