Targeting misfolding and aggregation of the amyloid-β peptide and mutant p53 protein using multifunctional molecules.

Abstract

Biomolecule misfolding and aggregation play a major role in human disease, spanning from neurodegeneration to cancer. Inhibition of these processes is of considerable interest, and due to the multifactorial nature of these diseases, the development of drugs that act on multiple pathways simultaneously is a promising approach. This Feature Article focuses on the development of multifunctional molecules designed to inhibit the misfolding and aggregation of the amyloid-β (Aβ) peptide in Alzheimer's disease (AD), and the mutant p53 protein in cancer. While for the former, the goal is to accelerate the removal of the Aβ peptide and associated aggregates, for the latter, the goal is reactivation via stabilization of the active folded form of mutant p53 protein and/or aggregation inhibition. Due to the similar aggregation pathway of the Aβ peptide and mutant p53 protein, a common therapeutic approach may be applicable.