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Yuca, E.

Publications and source records attributed to Yuca, E..

2 recordsLinked to original sources
bioRxiv2023

Highly Potent Peptide Therapeutics To Prevent Protein Aggregation In Huntington s Disease

Huntingtons disease (HD) is a progressive, autosomal dominant neurodegenerative disorder resulting from a significant amplification of CAG repeats in exon 1 of the Huntingtin (Htt) gene. More than 36 CAG repeats result in the formation of mutant Htt (mHtt) protein. These amino-terminal mHtt fragments lead to the formation of misfolded proteins, which then form aggregates in relevant brain regions. Available treatments concentrate primarily on alleviating the diseases symptoms. Therefore, therapies that can delay the progression of the disease are imperative to halt the course of the disease. Peptide-based drug therapies provide such a platform. Inhibitory peptides were screened against monomeric units of both wild type (Htt(Q25)) and mHtt fragments, including Htt(Q46)and Htt(Q103). It was accomplished by utilizing several display technologies. This study focuses on the in-vitro characterization of the screened peptides. Fibril kinetics was studied in real-time utilizing the Thioflavin T (ThT) assay. The impact of specific peptides on fibril formation was examined by observing the change in fluorescence signal. Atomic force microscopy was also used to study the influence of peptides on fibril formation. Three of the six chosen peptides (HHGANSLSLVSQD, HGLHSMHNKLTR, and WMFPSLKLLDYH) effectively inhibited aggregation. These experiments demonstrate that the chosen peptides suppress the formation of fibrils in mHtt proteins and can provide a therapeutic lead for further optimization and development.

neuroscience↗
bioRxiv2020

Binding Behavior of Microbial Functional Amyloidson Solid Surfaces

Self-assembling protein subunits hold great potential as biomaterials with improved functions. Among the self-assembled protein structures functional amyloids are promising unique properties such as resistance to harsh physical and chemical conditions their mechanical strength, and ease of functionalization. Curli proteins, which are functional amyloids of bacterial biofilms can be programmed as intelligent biomaterials. In order to obtain controllable curli based biomaterials for biomedical applications, and to understand role of each of the curli forming monomeric proteins (namely CsgA and CsgB from Escherichia coli) we characterized their binding kinetics to gold, hydroxyapatite, and silica surfaces. We demonstrated that CsgA, CsgB, and their equimolar mixture have different binding strengths for different surfaces. On hydroxyapatite and silica surfaces, CsgB is the crucial element that determines the final adhesiveness of the CsgA-CsgB mixture. On the gold surface, on the other hand, CsgA controls the behavior of the mixture. Those findings uncover the binding behavior of curli proteins CsgA and CsgB on different biomedically valuable surfaces to obtain a more precise control on their adhesion to a targeted surface.

microbiology↗