Aggregation characteristics of non-aromatic polar amino acids and its association to amyloids

Aggregation of amino acids to amyloid like structures is known to have implications in the pathophysiology of single amino acid based inborn-errors of metabolism (IEMs). Studying the aggregation properties of amino acids is of crucial interest also to understand the etiology of these IEMs from an amyloid perspective. Hence, herein we have studied the self-assembly of different non-aromatic charged/uncharged polar amino acids namely L-Glutamine (Gln), L-Aspartic acid (Asp) L-Glutamic acid (Glu) L-Histidine (His), L-Arginine (Arg), L-Serine (Ser) and L-Threonine (Thr) whose amyloid characteristics have still not been explored by ageing them in aqueous solution for varying time intervals from 0-15 days.. Notably, of all amino acids glutamine revealed amyloid like fibrillar morphologies as observed in case of aromatic amino acids reported previously after ageing. Further, aspartic acid and glutamic acids also revealed uniform self-assembled morphologies after 10 days of ageing. The MTT assay also corroborated with microscopic observations and a relatively more cytotoxic nature of glutamine assemblies as compared to other amino acids could also be envisaged. The Thioflavin T binding assays suggest the structures formed by Gln, Asp and Glu may have amyloid nature. Hence, the results presented in this manuscript may have crucial implications in understanding the patho-physiology of IEMs caused by the excess of Gln, Asp and Glu and suggest a possible extension of generic amyloid hypothesis to these diseases.