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

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Dec 20

PMID 38116434

Authors

Anooshay Khan

Cemile Elif Ozcelik

Ozge Begli

Oguzhan Oguz

Mehmet Seckin Kesici

Talip Serkan Kasirga

Salih Ozcubukcu

Esra Yuca

Urartu Ozgur Safak Seker

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications.

Mani Giri P, Banerjee A, Ghosal A, Layek B Int J Mol Sci. 2024; 25(7).

PMID: 38612804 PMC: 11011898. DOI: 10.3390/ijms25073995.

Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.

Tong H, Yang T, Xu S, Li X, Liu L, Zhou G Int J Mol Sci. 2024; 25(7).

PMID: 38612657 PMC: 11011923. DOI: 10.3390/ijms25073845.

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