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Highly Potent Peptide Therapeutics To Prevent Protein Aggregation in Huntington's Disease

Huntington's disease (HD) is a 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 a mutant Htt (mHtt) protein. These amino-terminal mHtt fragments lead to the formation of misfolded proteins, which then form aggregates in the relevant brain regions. Therapies that can delay the progression of the disease are imperative to halting 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, Htt(Q46) and Htt(Q103). Fibril kinetics was studied by utilizing the Thioflavin T (ThT) assay. Atomic force microscopy was also used to study the influence of the peptides on fibril formation. 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.

 

Comments:

The research you've summarized sounds promising in the quest to combat Huntington's disease (HD). Using peptide-based drug therapies to target the formation of misfolded proteins associated with mHtt fragments is a notable approach. The strategy of inhibitory peptides, especially those that can suppress fibril formation in mutant Huntingtin proteins, holds significant potential as a therapeutic avenue.

The use of Thioflavin T assay to study fibril kinetics is a well-established method to monitor amyloid formation, while atomic force microscopy provides detailed insights into the structural aspects of protein aggregates.

Identifying peptides that can effectively suppress fibril formation in mHtt proteins is a crucial step toward developing therapies that could potentially slow down the progression of HD. However, further optimization and development are essential to ensure the safety, efficacy, and practicality of these peptide-based drugs for clinical applications.

This research lays a foundation for future investigations and advancements in therapeutic interventions for Huntington's disease. If these findings can be translated into clinical applications, it could significantly impact the management and potentially the progression of this neurodegenerative disorder.

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S6825 Thioflavine S Thioflavine S (Thioflavin S, Direct Yellow 7) is a fluorogenic compound which becomes fluorescent only after oxidation. Thioflavine S is used as a fluorescent histochemical marker of dense core senile plaques.Thioflavine S can bind to dense-core amyloid-β deposits.

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