Study of inhibition of Aβ42 aggregation and oligomer forming with Docking and MD simulation

Alzheimer’s disease (AD) is the most common type of dementia in the elderly. The neuropathology and treatment of AD is not precisely determined yet, but according to the pathological studies, AD is associated with presence of toxic soluble oligomers and insoluble senile plaques formed by amyloidosis of Amyloid Beta (Aβ) in neocortical region of brain. The V10HHQKLVFFAE22 is a critical region of Aβ42 which facilitates aggregation process. An attractive therapeutic approach to treat AD is to identify small ligands that are capable of binding to critical residues in order to inhibit or reverse Aβ amyloidosis process as source of neurotoxicity. In this area, therapeutic efforts designed various organic agents and most of them focused on the N-terminal sequence of Aβ. Here, a peptide inhibitor derived from the C-terminal of Aβ (G33LMVG37) is utilized as inhibitor and combined Docking and Molecular dynamics simulation used to find the binding sights in the critical region (V10HHQKLVFFAE22). The simulation identified tree stable binding sites for Aβ42 inhibition by penta peptide. This result indicate that this penta-peptide is capable to inhibit aggregation process and can be consider as an drug for AD preclinical studies.