Therapeutic Peptides: A Promising Frontier in Huntington’s Disease Treatment

Huntington’s disease is a neurodegenerative genetic disorder characterized by a mutation in the huntingtin (HTT) gene, resulting in the production of a mutant huntingtin protein (mHTT).  The accumulation of mHTT leads to the development of toxic aggregates in neurons, causing cell dysfunction and eventual cell death.   Peptide therapeutics can target various aspects of HD pathology, including mHTT reduction and aggregation inhibition, extended CAG mRNA degradation, and modulation of dysregulated signaling pathways, such as BDNF/ TrkB signaling.  In addition, peptide therapeutics also target the detrimental interactions of mHTT with InsP3R1, CaM, or Caspase-6 proteins to mitigate HD.

A recent review in the Journal of Medicinal Chemistry by Ahamad et al provides a detailed perspective on anti-HD therapeutic peptides, highlighting their design, structural characteristics, neuroprotective effects, and specific mechanisms of action.  Peptide therapeutics for HD exhibit promise in preclinical models, although no approved peptide therapy for HD currently exists.

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