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, Wen-Xia Zhou and Yong-Xiang Zhang
Affiliation:
Keywords:
Alzheimer’s disease, combinational target, molecular network, senescence-accelerated mouse, traditional Chinese
medicine.
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.
