Gallic acid: A naturally occurring bifunctional inhibitor of amyloid and metal induced aggregation with possible implication in metal-based therapy

Abstract

Metal ions play a vital role in the aggregation of proteins by interfering with their correct folding, thereby affecting protein homeostasis and cell viability, leading to neurodegenerative diseases like Alzheimer's and Parkinson's. Development of therapeutics against protein misfolding diseases has become one of the widely studied areas of research. Till date, all advances in neurodegenerative diseases' therapeutics help symptomatically but do not prevent the root cause of the disease, i.e., the aggregation of protein involved in the diseases. Recent studies show a promising potential for metal based therapy utilising metal chelators. In this regard, we aimed to study the behaviour of gallic acid, a well characterised anti-aggregation compound, towards inhibition of metal-induced aggregation of a model enzyme, the human lysozyme. Using various spectroscopic and microscopic techniques we show that gallic acid inhibits metal induced aggregation. We delineate that gallic acid inhibits metal-induced aggregation by chelating the metal ions in the solvent, thereby inhibiting the aggregation of human lysozyme as demonstrated by our spectroscopic results which showed the formation of a complex between Mg2+ and gallic acid. Our studies showed retention of lysozymal activity upto 63.2% in presence of gallic acid. Our study therefore shows that gallic acid exhibits bifunctional inhibitory roles i.e., as an anti amyloidogenic and metal induced aggregation inhibitor. Due to its metal chelating activity, gallic acid can be further developed in metal based therapy against neurodegenerative diseases.