Self-assembly of Homogentisic acid may have implications in Alkaptonuria

31 May 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Alkaptonuria is a rare inborn-error of metabolism caused by the accumulation of Homogentisic acid (HA).. Herein, we have studied the self-assembling and aggregation properties of HA with the aim to assess the effect of accumulation of HA inside the body. To our surprise, we noted aggregation of HA follows an amyloidogenic pathway and the fibrillar assemblies made from small globules are formed after ageing HA solution. These assemblies were characterized by conventional microscopy tools and their amyloidogenic nature was assessed by Thioflavin T binding assays. The cytotoxicity analysis by MTT assay suggest cellular viability was decreased in both mouse neuronal and normal fibroblast cells when they were co-incubated with the aged solution of HA. Hence, the results presented in the manuscript are of significant interest in understanding the etiology of alkaptonuria form an amyloid perspective and may have possible implication in its therapeutic cure in future

Keywords

self-assembly
Homogentisic acid
amyloid

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