Nat Commun: How does Pytha Russell inhibit A-beta 42 accumulation?

Alzheimer's disease is characterized by memory loss and cognitive impairment.
AD is the leading cause of dementia, affecting more than 50 million people worldwide and is expected to exceed 150 million by 2050.
42 residual isomers of amyloid-β (A beta) peptides can be self-assembled into insoluble polymers, which are thought to be at the heart of the molecular pathway that causes AD.
, it is important to understand the aggregation process of A beta 42 at the molecular level in order to develop effective treatment strategies designed to inhibit its self-assembly.
20 years, people have been working to develop compounds that interfere with protein misfolding build-up.
, so far, no drugs have been used in the clinical use of these diseases.
of the main reasons for this failure is that we do not fully understand the process by which small molecules interact with protein aggregates and interfere with their aggregation.
Recently, using the single-molecule morphology and chemical sensitivity of the infrared nanospectral, researchers directly measured for the first time the structure and interaction between a single A-beta-42 lycopular and fibrous species and the aggregation inhibitor Pytha Russell, which prevents a beta-42 aggregation in-body and reverses its neurotoxicity in cellular and animal models of Alzheimer's disease.
results show that the compound's carboxyl interacts with A-beta 42 aggregates through a single hydrogen bond.
results establish infrared nanospectroscopy as a powerful tool for structural drug discovery for diseases caused by protein misfolding.