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

Area of Science:

• Biochemistry and Molecular Biology
• Medicinal Chemistry
• Neuroscience and Oncology

Background:

• Biomolecular misfolding and aggregation are implicated in severe human diseases, including neurodegenerative disorders and cancer.
• Developing drugs that target multiple disease pathways simultaneously is a promising therapeutic strategy due to the multifactorial nature of these conditions.

Purpose of the Study:

• To explore the development of multifunctional molecules for inhibiting amyloid-beta (Aβ) peptide misfolding and aggregation in Alzheimer's disease (AD).
• To investigate the use of these molecules for mutant p53 protein stabilization and aggregation inhibition in cancer therapy.
• To identify a common therapeutic approach for AD and cancer based on similar protein aggregation pathways.

Main Methods:

• Design and synthesis of multifunctional molecules.
• In vitro and in vivo studies to assess inhibition of Aβ peptide aggregation.
• Evaluation of mutant p53 protein stabilization and aggregation inhibition.
• Comparative analysis of aggregation pathways for Aβ peptide and mutant p53 protein.

Main Results:

• Demonstrated efficacy of multifunctional molecules in inhibiting Aβ peptide aggregation and promoting clearance.
• Showcased the potential of these molecules in stabilizing active mutant p53 protein and/or inhibiting its aggregation.
• Highlighted the conserved nature of aggregation pathways, suggesting a unified therapeutic strategy.

Conclusions:

• Multifunctional molecules represent a viable therapeutic strategy for both Alzheimer's disease and cancer.
• Targeting protein misfolding and aggregation offers a promising avenue for treating complex diseases.
• The development of single agents acting on multiple targets can overcome the limitations of traditional monotherapies.