Exploring therapeutic strategies based on chaperon-mediated disaggregation.

Abstract

In the quest to develop effective therapeutic strategies for diseases associated with protein misfolding and aggregation, molecular chaperones have emerged as pivotal players. This chapter explores the role of chaperones, such as Hsp40, Hsp70, and Hsp90, in mediating the disaggregation of misfolded proteins and facilitating proper folding under stress conditions. Despite their lack of sequence specificity, these proteins adeptly recognize exposed hydrophobic regions in partially folded states, thereby preventing aggregation and promoting functional conformations. The intricate network of chaperone interactions is crucial for maintaining cellular homeostasis and mitigating the pathological consequences of protein misfolding, particularly in conditions like Alzheimer's disease and various cancers. Innovative therapeutic approaches, including the use of pharmacological and chemical chaperones, aim to restore functionality to mutated or misfolded proteins, exemplified by interventions targeting the ΔF508 mutation in CFTR. While promising, the modulation of chaperone activity must be carefully calibrated to avoid disrupting cellular functions. This chapter highlights the potential of chaperone-mediated disaggregation as a therapeutic strategy, addressing both the current advancements and the challenges that lie ahead in harnessing these proteins for clinical benefit.