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

Date

2023-01-01

Author

Khan, Anooshay
Özçelik, Cemile Elif
Begli, Ozge
Oguz, Oguzhan
Kesici, Mehmet Seçkin
Kasırga, Talip Serkan
Özçubukçu, Salih
YÜCA YILMAZ, Esra
Seker, Urartu Ozgur Safak

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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.

Subject Keywords

Htt aggregation, Huntingtin, Huntington’s Disease, Inhibition, Peptide-based drug therapy

URI

https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85179170520&origin=inward
https://hdl.handle.net/11511/106659

Collections

Department of Chemistry, Article