An ortho-Iminoquinone Compound Reacts with Lysine Inhibiting Aggregation while Remodeling Mature Amyloid Fibrils
- PMID: 28425704
- DOI: 10.1021/acschemneuro.7b00017
An ortho-Iminoquinone Compound Reacts with Lysine Inhibiting Aggregation while Remodeling Mature Amyloid Fibrils
Abstract
Protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. It has been shown that lysine residues play a key role in the formation of these aggregates. Thus, the ability to disrupt aggregate formation by covalently modifying lysine residues could lead to the discovery of therapeutically relevant antiamyloidogenesis compounds. Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit amyloid aggregation. Using alpha-synuclein and Aβ1-40 as model amyloidogenic proteins, we observed that IQ was able to react with lysine residues and reduce amyloid aggregation. We also observed that IQ reacted with free amines within the amyloid fibrils preventing their dissociation and seeding capacity.
Keywords: Alzheimer’s disease; Imine; Parkinson’s disease; alpha-synuclein; amyloid aggregation; cross-link.
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