Small Molecule "Molecular Tweezers" that Inhibit Amyloid-β Fiber Formation

Alzheimer’s disease (AD) is an incurable neurodegenerative disease afflicting millions of Americans. Managed care of AD patients presents an enormous financial and social burden on society. Contributing to this burden is the dearth of effective treatments for AD. Current therapies target the symptoms rather than the cause of disease, which involves the deposition of the amyloid-beta (Aβ) and tau proteins into fibrous plaques or tangles in the brain. Aggregation of Aβ and tau proteins is neurotoxic, precipitates neuronal death and impairs cognitive signaling, all of which are characteristic of AD.

Therapeutic research efforts in AD continue to focus on the drivers of disease by targeting inhibition of Aβ production, enhancement of Aβ clearance, or disruption of Aβ assembly. Development of therapeutics had previously been hindered by our incomplete understanding of the disease. Recent studies, however, have greatly improved our understanding of the structure and the critical steps involved in the formation of the fibrous plaques. These findings are seeding the development of rationally designed therapies that target specific amino acids of Aβ fibers. Since they specifically target the disease mechanism, such approaches hold great promise for the treatment of AD.

• Inhibits the principle cause of AD instead of the symptoms.
• Disaggregates pre-existing Aβ40 and Aβ42 protein fibrils.
• The tweezer is non-toxic at concentrations up to 200 μM.