title: A Co-Module Regulated by Therapeutic Drugs in a Molecular Subnetwork of Alzheimer's Disease Identified on the Basis of Traditional Chinese Medicine and SAMP8 Mice.
abstract: There are currently no approved effective therapies for Alzheimer's disease (AD). AD is a classic, multifactorial, complex syndrome. Thus, a polypharmacological or multitargeted approach to AD might provide better therapeutic benefits than monotherapies. However, it remains elusive which biological processes and biomolecules involved in the pathophysiologic processes of AD would constitute good targets for multitargeted therapy. This study proposes that a co-module, consisting of biological processes, cellular pathways and nodes, in a molecular subnetwork perturbed by different therapeutic drugs may be the optimal therapeutic target for an AD multitarget-based intervention. Based on this hypothesis, genes regulated in the hippocampus and cortex of senescence-accelerated mouse prone-8 (SAMP8) mice by traditional Chinese medicine (TCM) prescriptions with different constituents and the same beneficial effects on AD, including the decoctions Liu-Wei-Di-Huang (LW), Ba-Wei-Di-Huang (BW), Danggui-Shaoyao-San (DSS), Huang-Lian-Jie-Du (HL) and Tiao-Xin-Fang (TXF), were investigated via cDNA microarray, and the perturbed subnetworks were constructed and interpreted. After comparing 15 perturbed subnetworks based on genes affected by LW, BW, HL, DSS and TXF, the results showed that the most important common nodes perturbed by these interventions in the brains of SAMP8 mice were RPS6KA1 and FHIT, and that other important common nodes included UBE2D2, STUB1 and AMFR. These five drugs simultaneously and significantly disturbed the regulation of apoptosis and protein ubiquitination among biological processes. These nodes and processes were key components of the co-module regulated by therapeutic drugs in a molecular subnetwork of AD. These results suggest that targeting candidate regulator of apoptosis and protein ubiquitination might be effective for AD treatment, and that RPS6KA1, FHIT, UBE2D2, STUB1 and AMFR might be optimal combinational targets of an AD multitarget-based therapy.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Cheng
authors.forename: Xiu-Liang
authors.initials: XL
authors.lastname: Cui
authors.forename: Yue
authors.initials: Y
authors.lastname: Zheng
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Huang
authors.initials: H
authors.lastname: Huang
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Zhao
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Bo
authors.forename: Sheng-Qi
authors.initials: SQ
authors.lastname: Wang
authors.affiliation: Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. zhouwx@bmi.ac.cn.
authors.forename: Wen-Xia
authors.initials: WX
authors.lastname: Zhou
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015870:Gene Expression; D008297:Male; D051379:Mice; D046228:Microarray Analysis; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents