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ACS Chem Neurosci ; 8(8): 1704-1712, 2017 08 16.
Article in English | MEDLINE | ID: mdl-28425704

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 Aß1-40 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.


Subject(s)
Amyloid beta-Peptides/metabolism , Neuroprotective Agents/pharmacology , Peptide Fragments/metabolism , Protein Aggregation, Pathological/drug therapy , Quinones/pharmacology , alpha-Synuclein/metabolism , Animals , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/toxicity , Cell Survival/drug effects , Cells, Cultured , Chickens , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , HEK293 Cells , Humans , Lysine/metabolism , Methionine/metabolism , Mice , Micrococcus luteus , Microtubule-Associated Proteins/metabolism , Muramidase/metabolism , Neuroprotective Agents/toxicity , Oxidation-Reduction , Protein Aggregation, Pathological/metabolism , Quinones/toxicity , Tyrosine 3-Monooxygenase/metabolism
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