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

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

Volume: 12 Issue: 9

Author(s): Xiao-Rui Cheng, Xiu-Liang Cui, Yue Zheng, Gui-Rong Zhang, Peng Li, Huang Huang, Yue-Ying Zhao, Xiao-Chen Bo, Sheng-Qi Wang and Wen-Xia Zhou and Yong-Xiang Zhang

Affiliation:

关键词: 老年痴呆，组合靶点，分子网络，加速衰老小鼠，中药。

摘要: 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.

Cite this article as:

Xiao-Rui Cheng, Xiu-Liang Cui, Yue Zheng, Gui-Rong Zhang, Peng Li, Huang Huang, Yue-Ying Zhao, Xiao-Chen Bo, Sheng-Qi Wang and Wen-Xia Zhou and Yong-Xiang Zhang , 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, Current Alzheimer Research 2015; 12 (9) . https://dx.doi.org/10.2174/1567205012666150710111858