Functional analysis and signaling pathway enrichment analysis of genes associated with Alzheimer’s disease and Parkinson’s disease

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer’s disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer’s disease.

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Network Pharmacology Study of Heat-Clearing and Detoxifying Traditional Chinese Medicine for Alzheimer's Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7831675 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Hongxing Li ◽

Xinyue Zhang ◽

Lili Gu ◽

Ningzi Wu ◽

Lingxi Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Chlorogenic Acid ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Pathway Enrichment Analysis

This study aims to explore the possible homologous mechanism of 7 frequently‐used herbs for heat-clearing and detoxification in traditional Chinese medicine (HDTCM) for treating Alzheimer's disease (AD), one of the most common types of dementia, based on network pharmacology. Herbs that satisfied the criteria of containing chlorogenic acid, relating to AD and aligning with HDTCM, were simultaneously collected to determine whether they have anti-AD effect based on a survey of the literature. Herb-ingredient-target-disease networks were constructed by collecting information from the TCMSP and GeneCards public databases. The common targets of the herbs and AD were identified for conducting a Gene Ontology (GO) analyses and a Reactome pathway enrichment analysis. The results showed that PTGS1, IL-6, CASP3, and VEGFA were the predicted key gene targets. The IL-4 and IL-13 signaling pathway, the ESR-mediated signaling pathway, and the extranuclear estrogen signaling pathway were the significant pathways associated with the 7 herbs. This study revealed that the analogous anti-AD mechanism of the 7 herbs of HDTCM may be associated with anti-inflammation, which is a common effect of the chlorogenic acid and quercetin components.

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Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer’s Disease

Molecules ◽

10.3390/molecules24081499 ◽

2019 ◽

Vol 24 (8) ◽

pp. 1499 ◽

Cited By ~ 3

Author(s):

Yi-wei Sun ◽

Yue Wang ◽

Zi-feng Guo ◽

Kai-cheng Du ◽

Da-li Meng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Pathway Enrichment ◽

Large Numbers ◽

Brain Barrier Permeability ◽

Target Network ◽

Synergistic Mechanism

Ohwia caudata (OC)—a traditional Chinese medicine (TCM)—has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer’s disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood–brain barrier permeability against AD, by using a system network level-based in silico approach. The results revealed that two new flavonoids, and another 26 compounds isolated from OC in our lab, were highly connected to AD-related signaling pathways and biological processes, which were confirmed by compound–target network, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, respectively. Predicted by the virtual screening and various network pharmacology methods, we found the multiple mechanisms of OC, which are effective for alleviating AD symptoms through multiple targets in a synergetic way.

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MicroRNA-Target Interaction Regulatory Network in Alzheimer’s Disease

Journal of Personalized Medicine ◽

10.3390/jpm11121275 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1275

Author(s):

Aleksander Turk ◽

Tanja Kunej ◽

Borut Peterlin

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Interaction Analysis ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Microrna Target ◽

Target Interaction ◽

Pathway Enrichment ◽

Protein Protein Interaction

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on miRNA–target interactions (MTI) associated with AD are scattered across databases and publications, thus making the identification of promising miRNA biomarkers for AD difficult. In response to this, a list of experimentally validated AD-associated MTIs was obtained from miRTarBase. Cytoscape was used to create a visual MTI network. STRING software was used for protein–protein interaction analysis and mirPath was used for pathway enrichment analysis. Several targets regulated by multiple miRNAs were identified, including: BACE1, APP, NCSTN, SP1, SIRT1, and PTEN. The miRNA with the highest numbers of interactions in the network were: miR-9, miR-16, miR-34a, miR-106a, miR-107, miR-125b, miR-146, and miR-181c. The analysis revealed seven subnetworks, representing disease modules which have a potential for further biomarker development. The obtained MTI network is not yet complete, and additional studies are needed for the comprehensive understanding of the AD-associated miRNA targetome.

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PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.648636 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hui-Zhi Long ◽

Yan Cheng ◽

Zi-Wei Zhou ◽

Hong-Yu Luo ◽

Dan-Dan Wen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Natural Products ◽

Signaling Pathway ◽

Glycogen Synthase ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Gsk 3Β

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3β (GSK-3β), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.

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Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190717124507 ◽

2019 ◽

Vol 22 (6) ◽

pp. 411-420 ◽

Cited By ~ 5

Author(s):

Xian-Jun Wu ◽

Xin-Bin Zhou ◽

Chen Chen ◽

Wei Mao

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Diseases ◽

Signaling Pathway ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Pathway Enrichment ◽

Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

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Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666191112124435 ◽

2020 ◽

Vol 18 (10) ◽

pp. 758-768 ◽

Cited By ~ 2

Author(s):

Khadga Raj ◽

Pooja Chawla ◽

Shamsher Singh

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Syndrome ◽

Dopamine Synthesis ◽

Synthetic Analog

: Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s Disease (PD).

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