title: Uncovering the Molecular Mechanism of Actions between Pharmaceuticals and Proteins on the AD Network.
abstract: This study begins with constructing the mini metabolic networks (MMNs) of beta amyloid (Aβ) and acetylcholine (ACh) which stimulate the Alzheimer's Disease (AD). Then we generate the AD network by incorporating MMNs of Aβ and ACh, and other MMNs of stimuli of AD. The panel of proteins contains 49 enzymes/receptors on the AD network which have the 3D-structure in PDB. The panel of drugs is formed by 5 AD drugs and 5 AD nutraceutical drugs, and 20 non-AD drugs. All of these complexes formed by these 30 drugs and 49 proteins are transformed into dyadic arrays. Utilizing the prior knowledge learned from the drug panel, we propose a statistical classification (dry-lab). According to the wet-lab for the complex of amiloride and insulin degrading enzyme, and the complex of amiloride and neutral endopeptidase, we are confident that this dry-lab is reliable. As the consequences of the dry-lab, we discover many interesting implications. Especially, we show that possible causes of Tacrine, donepezil, galantamine and huperzine A cannot improve the level of ACh which is against to their original design purpose but they still prevent AD to be worse as Aβ deposition appeared. On the other hand, we recommend Miglitol and Atenolol as the safe and potent drugs to improve the level of ACh before Aβ deposition appearing. Moreover, some nutrients such as NADH and Vitamin E should be controlled because they may harm health if being used in wrong way and wrong time. Anyway, the insights shown in this study are valuable to be developed further.
authors.affiliation: College of Mathematical Sciences and LPMC, Nankai University, Tianjin, PRC.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Cao
authors.affiliation: College of Mathematical Sciences and LPMC, Nankai University, Tianjin, PRC.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Internal Medicine for the Heart, Tianjin University of Traditional Chinese Medicine, Tianjin, PRC.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Mao
authors.affiliation: National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, PRC.|High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biomedicine, TEDA, Tianjin, PRC.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Mathematical Sciences and LPMC, Nankai University, Tianjin, PRC.|State Key Laboratory for Medical Chemical and Biology, Nankai University, Tianjin, PRC.
authors.forename: Jishou
authors.initials: J
authors.lastname: Ruan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D004364:Pharmaceutical Preparations; D011506:Proteins