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 (Aβ), a biomarker for AD progression, has been shown. Nodes represent the entities and edges represent the relation (interactions) of one node to another node. Aβ 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 Aβ in presence of SPIONs. This study may lead to better understanding, which is required to target the metabolism of Aß peptide, a pivotal player in this pathology.

Designing of CD8⁺ and CD8⁺-overlapped CD4⁺ epitope vaccine by targeting late and early proteins of human papillomavirus

“…75 Nodes in the pathway represented the entities, and edges represented connectivity of one node to another, which was closely related to each other. 76 The inhibitory concentration (1 µg) of proposed peptides was collected from the published experimental data and pharmacokinetic studies. 64 Mass action kinetics (V=KΠi S) was applied for pharmacokinetic study.…”

“…In addition, the CAVPVTTRY 4-12 epitope of E4 protein was predicted to have binding affinity for HLA-(A*29, A*30, B*58, B*35) allotypes (Table 1C). Among the five epitopes of E6 protein, RTEVYQFAF [41][42][43][44][45][46][47][48][49] and YSRIRE-LRY [72][73][74][75][76][77][78][79][80] were predicted to have binding affinity for HLA-A*(32:01, 29:02) and HLA-B*58: 01 MHC class I alleles (Table 1D). Out of 13 MHC-binding E7 peptides (Table 1E), STLSFVCPW [93][94][95][96][97][98][99][100][101] (HLA-A*32:01, HLA-B*58:01, HLA-B*57:01), LQQLFLSTL [87][88][89][90][91][92][93][94][95] (HLA-A*02:06), and QLFLSTLSF [89][90][91][92][93][94][95][96]…”

“…. Among these, the LTAE-VMSYI[68][69][70][71][72][73][74][75][76] demonstrated interactions with six alleles, viz, HLA-A*(68:02, 02:06, 02:01), HLA-B*58: 01, and HLA-C*(12:03, 15:02). In addition, 12 out of 17 epitopes of L2 protein, KRASATDLY 10-18 , STSFTNPAF 154-162 , FSDPSIIEV 162-170 , LVTFDNPAY 248-256 , HSDFMDIIR 273-281 , QIGGRVHFY 312-320 , ATDLYKTCK[14][15][16][17][18][19][20][21][22] , STINKSFTY 362-370 , MPSTAASSY 377-385 , TSAWDVPIY 393-401 , PTNAAT-STY 420-428 , and QYYLWPWYY 435-443 , exhibited significant binding affinity for the HLA alleles.…”

A comparative chemogenic analysis for predicting Drug-Target Pair via Machine Learning Approaches

“…In general, the interactions are predicted by using the fact of similarity between the proteins and ligands 32 . In case of the less number of reported ligands per protein, the result of the ligand-based approach may be ambiguous 33 .The second approach is the docking approach, a 3D structure of the drug and a protein is taken and then a simulation program is run to determine whether they can interact or not [34][35][36][37] . However, some proteins with unknown 3D structures are there to which docking cannot be applied.…”

“…The second approach is the docking approach, a 3D structure of the drug and a protein is taken and then a simulation program is run to determine whether they can interact or not [34][35][36][37] . However, some proteins with unknown 3D structures are there to which docking cannot be applied.…”