Sharif Digital Repository

According to the Amyloid hypothesis, as the foremost scientific explanation for Alzheimer Disease (AD), the neuropathology of AD is related to toxic fragments of amyloid beta (Aβ) protein. Based on this hypothesis, an attractive therapeutic approach was demonstrated to identify multifunctional peptides able to modulate Aβ pathologies as the source of AD. On this premise, a bifunctional polypeptide based on the iAβ5p lead compound, was designed to inhibit Aβ aggregation and free metal ions. Herein, the efficacy of this novel drug in Zn2+ and Cd2+ ion chelation was examined through an integrated technique comprising combined Docking, QM, and MD simulations. MD relaxation of a set of probable... 

Zinc binding to β-amyloid structure could promote amyloid-β aggregation, as well as reactive oxygen species (ROS) production, as suggested in many experimental and theoretical studies. Therefore, the introduction of multifunctional drugs capable of chelating zinc metal ion and inhibiting Aβ aggregation is a promising strategy in the development of AD treatment. The present study has evaluated the efficacy of a new bifunctional peptide drug using molecular docking and molecular dynamics (MD) simulations. This drug comprises two different domains, an inhibitor domain, obtained from the C-terminal hydrophobic region of Aβ, and a Zn2+ chelating domain, derived from rapeseed meal, merge with a... 

Alzheimer’s disease (AD) is an irreversible neurological disorder that progresses gradually and can cause severe cognitive and behavioral impairments. This disease is currently considered a social and economic incurable issue due to its complicated and multifactorial characteristics. Despite decades of extensive research, we still lack definitive AD diagnostic and effective therapeutic tools. Consequently, one of the most challenging subjects in modern medicine is the need for the development of new strategies for the treatment of AD. A large body of evidence indicates that amyloid-β (Aβ) peptide fibrillation plays a key role in the onset and progression of AD. Recent studies have reported...