Open AccessEye lens crystallin proteins inhibit the autocatalytic amyloid amplification nature of mature α-synuclein fibrils
Author(s) -
Ricardo Gaspar,
Tommy Garting,
Anna Stradner
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0235198
Subject(s) - crystallin , fibril , biophysics , protein aggregation , chemistry , autocatalysis , protein folding , nucleation , kinetics , chaperone (clinical) , amyloid (mycology) , neurite , biochemistry , microbiology and biotechnology , biology , in vitro , medicine , inorganic chemistry , physics , organic chemistry , pathology , quantum mechanics , catalysis
Parkinson´s disease is characterized by the accumulation of proteinaceous aggregates in Lewy bodies and Lewy Neurites. The main component found in such aggregates is α-synuclein. Here, we investigate how bovine eye lens crystallin proteins influence the aggregation kinetics of α-synuclein at mildly acidic pH (5.5) where the underlying aggregation mechanism of this protein is dominated by secondary nucleation of monomers on fibril surface providing an autocatalytic amyloid amplification process. Bovine α-, β H - and γ B -crystallins were found to display chaperone-like activity inhibiting α-synuclein aggregation. This effect was shown to be time-dependent, with early additions of α-crystallin capable of retarding and even inhibiting aggregation during the time frame of the experiment. The inhibitory nature of crystallins was further investigated using trap and seed kinetic experiments. We propose crystallins interact with mature α-synuclein fibrils, possibly binding along the surfaces and at fibril free ends, inhibiting both elongation and monomer-dependent secondary nucleation processes in a mechanism that may be generic to some chaperones that prevent the onset of protein misfolding related pathologies.