Inhibitory Effects of an Anti-Amyloid Small Molecule on Double- Horseshoe Structure of Aβ

Alzheimer’s Disease (AD) is a neurodegenerative debilitating human condition in which short 40 to 42 residue peptides, known as Amyloid β, undergo conformational and structural changes and consequently form amyloid oligomers and fibrils. Although various inhibitors have been studied in vitro and in silico against amyloid fibrillation, there has not been a magic drug for treatment of AD. Among these inhibitors, RS-0406 is one of the promising pyridazine based inhibitors which is under consideration in the phaseⅡ of clinical trial. In this work, we performed Molecular Dynamics (MD) simulations to better investigate at the atomic level mechanism of Aβ inhibition. Using bothdocked and randomly positioned RS-0406 molecules with S-shaped model of Aβ which is more disease relevant, important interactions of the drug were observed. The interactions include H-bond formation and non-covalent polar and non-polar interactions with backbones and sidechains mostly near the amyloidogenic regions. These interactions may compete with interstrand interactions in amyloidogenic regions

کلیدواژه ها:

Alzheimer’s Disease ، Amyloid β ، Neurodegenerative ، Inhibitor ، Pyridazine