Amyloids are fibril-like protein aggregates enriched in β-sheet content associated with diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (HD). Fibrils form from a variety of precursor oligomers. Both fibrils and oligomers are linked to cellular toxicity; therefore, a therapeutic strategy is preventing aggregate formation with small molecules. While aggregation inhibitors are numerous, they often lose efficacy in complex cellular environments. One cellular factor that interferes with aggregate inhibition is the presence of lipid membranes. The purpose of the experiment is to validate that specific small molecules work to prevent fibril formation and to observe the effects of them in a complex lipid environment. To accomplish this, a mutant huntingtin (htt) protein was used as the experimental system. Several known amyloid inhibitors, epigallocatechin-3-gallate (EGCG), curcumin, riluzole, and congo red, were tested using atomic force microscopy (AFM) and thioflavin T assays (ThT) to determine their efficacy in reducing fibril formation. Additionally, their ability to alter phenotype in a <i>C. elegans</i> model of HD was investigated. Each of the small molecules decreased fibril formation in the absence of lipids; however, lipid vesicles influenced the process. Based on initial observations, each drug improved the thrashing phenotype in <i>C. elegans</i>.

Inhibiting fibril aggregates that occur in Huntington’s disease

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