In silico designing of putative peptides for targeting pathological protein Htt in Huntington's disease

Abstract

Huntington's disease is a neurodegenerative disease caused by CAG repeat in the first exon of HTT (Huntingtin) gene, leading to abnormal form of Htt protein containing enlarged polyglutamine strands of variable length that stick together to form aggregates and is toxic to brain causing brain damage. Complete reversal of brain damage is not possible till date but recovery may be possible by peptide therapy. The peptide-based therapy for Huntington's disease includes both poly Q peptide as well as non poly Q peptides like (QBP1)2, p42, Exendin 4, ED11, CaM, BiP, Leuprorelin peptide. The novel approach that is currently being tested in this article is the peptide-based therapy to target the mutated protein. This approach is based on the principle of preventing the aggregation of mutant Htt by blocking the potential sites responsible for protein aggregation and thereby ameliorating the disease symptoms. Herein, we have screened a variety of potential peptides that were known to prevent the protein aggregation, comparatively analyzed their binding affinity with homology modeled Htt protein, designed novel peptides based upon conservation analysis among screened potential peptides as a therapeutic agent, comparatively analyzed the therapeutic potential of novel peptides against modeled Htt protein for investigating the therapeutic prospects of Huntington's disease. We have designed a peptide for the therapy of Huntington's disease by comparing several peptides, which are already in use for Huntington's disease.

Keywords

• Huntington's disease
• Htt protein
• Peptide-based therapy
• Polyglutamine disorders
• Neurodegenerative disease