posted on 2023-11-14, 17:08authored byAnooshay Khan, Cemile Elif Özçelik, Ozge Begli, Oguzhan Oguz, Mehmet Seçkin Kesici, Talip Serkan Kasırga, Salih Özçubukcu, Esra Yuca, Urartu Ozgur Safak Seker
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.