Gelsolin protein: aggregation and inhibition of disease-relevant peptides Carlos Quintero Arias, Sanela Martic Trent University, Canada Gelsolin is a protein responsible for the remodelling of the actin cytoskeleton1. Under pathological conditions, Gelosolin is susceptible to cleavage and subsequent aggregation1,2. The D187N and D187Y point mutations have been associated with fragmentation and formation of amyloidogenic 8kDa (173–242) and 5 kDa (173– 225) fragments2. The fragments systematically deposit within the organs to promote cell death2. Despite the detrimental effects of Gelsolin mutation, the disease mechanism is understudied. Herein, we investigated the aggregation propensities, inhibition, and morphology of wild-type Gelsolin peptides (187-193) and their associated mutants under physiological conditions. Biophysical methods allowed for the identification and visualization of protein aggregates and amyloids. We reported that CFILDL-containing peptides were prone to aggregation, which may be inhibited and reversed with small molecules. Of note is the unique behaviour of peptide mutants with respect to their aggregation propensities pointing to their biological relevance. Treating aberrant Gelsolin aggregates may be a foundation for improving outcomes of similar amyloidogenic diseases. References 1. Ahmad, M., Esposto, J., Golec, C., Wu, C., & Martic-Milne, S. (2021). Aggregation of gelsolin wild-type and G167K/R, N184K, and D187N/Y mutant peptides and inhibition. Molecular and Cellular Biochemistry, 476, 2393–2408. https://doi. org/10.1007/s11010-021-04085-6 2. Solomon, J. P., Page, L. J., Balch, W. E., & Kelly, J. W. (2012). Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention. Critical Reviews in Biochemistry and Molecular Biology, 47, 282–296. https:// doi.org/10.3109/10409238.2012.661401
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