Effects of Mutations and Post-Transla- tional Modifications on a-Synuclein In Vitro Aggregation

Fibrillar aggregates of the a-synuclein (alpha S) protein are the hallmark of Parkinson's Disease and related neurodegenerative disorders. Characterization of the effects of mutations and post-translational modifica-tions (PTMs) on the aS aggregation rate can provide insight into the mechanism of fibril formation, which remains elusive in spite of intense study. A comprehensive collection (375 examples) of mutant and PTM aggregation rate data measured using the fluorescent probe thioflavin T is presented, as well as a sum-mary of the effects of fluorescent labeling on aS aggregation (20 examples). A curated set of 131 single mutant de novo aggregation experiments are normalized to wild type controls and analyzed in terms of structural data for the monomer and fibrillar forms of alpha S. These tabulated data serve as a resource to the community to help in interpretation of aggregation experiments and to potentially be used as inputs for computational models of aggregation.(c) 2022 Elsevier Ltd. All rights reserved.