Deciphering the Biochemical Pathway and Pharmacokinetic Study of Amyloid βeta-42 with Superparamagnetic Iron Oxide Nanoparticles (SPIONs) Using Systems Biology Approach

Abstract

Alzheimer's disease (AD) pathogenesis leads to the appearance of senile plaques due to the production and deposition of the β-amyloid peptide (Aβ). Superparamagnetic iron oxide nanoparticles (SPIONs) have potential role in the detection and imaging of Aβ plaques in AD. SPIONs have shown appropriate potential in the diagnosis and treatment of AD. In the present study, the pharmacokinetics of SPIONs and its effect in the biochemical pathway of AD were analyzed using collected information. During analysis, the interaction of SPIONs with amyloid beta-42 (Aβ₄₂), a biomarker for AD progression, has been shown. Nodes represent the entities and edges represent the relation (interactions) of one node to another node. Aβ₄₂ and their interaction with other entities making up biochemical network are involved in AD mechanism in presence of SPION. The kinetic simulation was done to investigate pharmacokinetics of SPIONs for AD, where concentration was assigned of nanoparticles and other entities were applied as a kinetic irreversible simple Michaelis-Menten or mass action kinetics. Simulation was done in presence and absence of SPIONs to investigate pharmacokinetic effect in AD and explore the mechanism of Aβ₄₂ in presence of SPIONs. This study may lead to better understanding, which is required to target the metabolism of Aß₄₂ peptide, a pivotal player in this pathology.

Keywords: Alzheimer’s disease; Amyloid beta-42; Biochemical network; Pharmacokinetics; SPIONs.