miR-590-3 and SP1 Promote Neuronal Apoptosis in Patients with Alzheimer’s Disease via AMPK Signaling Pathway

Alzheimer’s disease (AD) is a progressive neurological degenerative illness with a hidden onset. Its pathogenesis is complicated, although with molecular biology research on cancer and targeted research on pathogenic mechanisms, good progress has not yet been made. Therefore, this work built a multifactor-driven neuronal apoptosis dysfunction module for the purpose of probing its underlying pathogenic mechanisms. We performed differential expression analysis, coexpression analysis, enrichment analysis, and hypergeometric tests to calculate the underlying regulatory effects of multifactors on the modules by the way of the whole gene expression profile of AD and identify a series of ncRNA (miR-320a) and TF (NFKB1). Additionally, we screened 10 modules corresponding to the Hub gene, which tend to regulate the physiological progress of inflammation, regulation of autophagy, cerebral cortex neuron differentiation, glial cell apoptotic, and so on. Meanwhile, Alzheimer’s disease is triggered by signaling pathways such as the MPK signaling pathway. In this study, a dysfunction module is utilized to verify that miR-590-3 and SP1 motility factors can regulate neurons in Alzheimer’s disease through the MPK signaling pathway, not only providing new insights into the pathogenesis of Alzheimer’s disease but also laying a solid theoretical foundation for the biologists to further cure Alzheimer’s disease.

Download Full-text

P2-316: Disturbance in AMP-activated protein kinase (AMPK) signaling pathway in Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2010.05.1367 ◽

2010 ◽

Vol 6 ◽

pp. S406-S406

Author(s):

Hyoung-Gon Lee ◽

Hyun-Pil Lee ◽

Wataru Kudo ◽

Xiongwei Zhu ◽

George Perry ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protein Kinase ◽

Signaling Pathway ◽

Ampk Signaling ◽

Amp Activated Protein Kinase

Download Full-text

Identification of hydatidosis-related modules and key regulatory genes

PeerJ ◽

10.7717/peerj.9280 ◽

2020 ◽

Vol 8 ◽

pp. e9280

Author(s):

Jijun Song ◽

Mingxin Song

Keyword(s):

Transcription Factors ◽

Signaling Pathway ◽

Target Genes ◽

Expression Profiles ◽

Differential Expression Analysis ◽

Interaction Network ◽

Enrichment Analysis ◽

Bmp Signaling ◽

Differentially Expressed ◽

Regulatory Effects

Background Echinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection. Method First, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism. Results A total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine. Conclusion The results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.

Download Full-text

Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer’s Disease Based on Network Pharmacology and Molecular Docking

BioMed Research International ◽

10.1155/2021/5418142 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yi Kuan Du ◽

Yue Xiao ◽

Shao Min Zhong ◽

Yi Xing Huang ◽

Qian Wen Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Signaling Pathway ◽

Target Prediction ◽

Enrichment Analysis ◽

The Elderly ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Active Components

Alzheimer’s disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer’s disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of “drug-active ingredient-ingredient target.” A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer’s disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer’s signal pathway, thus reducing the production of Aβ, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.

Download Full-text

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.

Download Full-text

Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats withAβ1–40-Induced Alzheimer’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/942917 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Hai-yan Hu ◽

Zhi-hui Cui ◽

Hui-qin Li ◽

Yi-ru Wang ◽

Xiang Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Signaling Pathway ◽

Learning And Memory ◽

Ming Dynasty ◽

Neuronal Apoptosis ◽

Caspase 3 ◽

Tunel Staining ◽

Apoptotic Signaling ◽

Chinese Herbal

Alzheimer’s disease (AD) is the most common form of dementia and lacks disease-altering treatments. Fumanjian (FMJ), a famous classic Chinese herbal prescription for dementia, was first recorded in theComplete Works of Jingyueduring the Ming Dynasty. This study aimed to investigate whether FMJ could prevent cognitive deficit and take neuroprotective effects inAβ1–40-induced rat model through apoptotic signaling pathway. AD model was established by bilateral injection ofAβ1–40into hippocampus in rat. All rats were tested for their capabilities of spatial navigation and memorization by Morris water maze. Apoptosis was tested using TUNEL staining in hippocampus neuronal cells; RT-PCR tested expression of Bcl-2 and Bax mRNA; western blotting tested protein level of cleaved caspase-3. After 14 days of treatment, FMJ significantly improved the escape latency and enhanced platform-cross number compared with theAβ1–40-injected group (P<0.05orP<0.01). FMJ also significantly decreased number of TUNEL-positive neuronal apoptosis and the expressions of Bax and cleaved Caspase-3 and increased the expression of Bcl-2 (P<0.01) compared with AD model group. In conclusion, FMJ exerts a protective effect againstAβ1–40-induced learning and memory deficits and neuronal apoptosis, suggesting that FMJ could be used as a potential therapeutic formula for AD.

Download Full-text

cAMP/PKA signaling pathway contributes to neuronal apoptosis via regulating IDE expression in a mixed model of type 2 diabetes and Alzheimer's disease

Journal of Cellular Biochemistry ◽

10.1002/jcb.26321 ◽

2017 ◽

Vol 119 (2) ◽

pp. 1616-1626 ◽

Cited By ~ 10

Author(s):

Huajie Li ◽

Song Yang ◽

Jian Wu ◽

Lei Ji ◽

Linfeng Zhu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Signaling Pathway ◽

Neuronal Apoptosis ◽

Mixed Model

Download Full-text

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

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2020-1-108-113 ◽

2020 ◽

Vol 19 (1) ◽

pp. 108-113

Author(s):

N. Yu. Chasovskikh ◽

A. Yu. Grechishnikova ◽

D. V. Smirnov

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Functional Analysis ◽

Parkinson's Disease ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Pathway Enrichment

Download Full-text

A Network Pharmacology Approach to Estimate Potential Targets of the Active Ingredients of Epimedium for Alleviating Mild Cognitive Impairment and Treating Alzheimer’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/2302680 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Xianwei Gao ◽

Shengnan Li ◽

Chao Cong ◽

Yuejiao Wang ◽

Lianwei Xu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Molecular Docking ◽

Mild Cognitive Impairment ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Active Ingredients ◽

Depth Analysis ◽

The Common

Background. The present study made use of a network pharmacological approach to evaluate the mechanisms and potential targets of the active ingredients of Epimedium for alleviating mild cognitive impairment (MCI) and treating Alzheimer’s disease (AD). Methods. The active ingredients of Epimedium were acquired from the Traditional Chinese Medicine System Pharmacology database, and potential targets were predicted using the TCMSP target module, SwissTargetPrediction, and PharmMapper database. Target proteins correlating with MCI and AD were downloaded from the GeneCards, DisGeNet, and OMIM databases. The common targets of Epimedium, MCI, and AD were identified using the Jvenn online tool, and a protein-protein interaction (PPI) network was constructed using the String database and Cytoscape. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the common targets was performed using DAVID, and molecular docking between active ingredients and target genes was modeled using AutoDock Vina. Results. A total of 20 active ingredients were analyzed, and 337 compound-related targets were identified for Epimedium. Out of 236 proteins associated with MCI and AD, 54 overlapped with the targets of Epimedium. The top 30 interacting proteins in this set were ranked by topological analysis. GO and KEGG enrichment analysis suggested that the common targets participated in diverse biological processes and pathways, including cell proliferation and apoptosis, inflammatory response, signal transduction, and protein phosphorylation through cancer pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, sphingolipid signaling pathway, FoxO signaling pathway, and TNF signaling pathway. Molecular docking analysis suggested that the 20 active ingredients could bind to the top 5 protein targets. Conclusions. The present study provides theoretical evidence for in-depth analysis of the mechanisms and molecular targets by which Epimedium protects against MCI, AD, and other neurodegenerative diseases and lays the foundation for pragmatic clinical applications and potential new drug development.

Download Full-text

Identification of Candidate Genetic Markers and a Novel 4-genes Diagnostic Model in Osteoarthritis through Integrating Multiple Microarray Data

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200428120310 ◽

2020 ◽

Vol 23 (8) ◽

pp. 805-813

Author(s):

Ai Jiang ◽

Peng Xu ◽

Zhenda Zhao ◽

Qizhao Tan ◽

Shang Sun ◽

...

Keyword(s):

Signaling Pathway ◽

Microarray Data ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Functional Enrichment ◽

Joint Disease ◽

Support Vector ◽

Diagnostic Model ◽

Data Sets

Background: Osteoarthritis (OA) is a joint disease that leads to a high disability rate and a low quality of life. With the development of modern molecular biology techniques, some key genes and diagnostic markers have been reported. However, the etiology and pathogenesis of OA are still unknown. Objective: To develop a gene signature in OA. Method: In this study, five microarray data sets were integrated to conduct a comprehensive network and pathway analysis of the biological functions of OA related genes, which can provide valuable information and further explore the etiology and pathogenesis of OA. Results and Discussion: Differential expression analysis identified 180 genes with significantly expressed expression in OA. Functional enrichment analysis showed that the up-regulated genes were associated with rheumatoid arthritis (p < 0.01). Down-regulated genes regulate the biological processes of negative regulation of kinase activity and some signaling pathways such as MAPK signaling pathway (p < 0.001) and IL-17 signaling pathway (p < 0.001). In addition, the OA specific protein-protein interaction (PPI) network was constructed based on the differentially expressed genes. The analysis of network topological attributes showed that differentially upregulated VEGFA, MYC, ATF3 and JUN genes were hub genes of the network, which may influence the occurrence and development of OA through regulating cell cycle or apoptosis, and were potential biomarkers of OA. Finally, the support vector machine (SVM) method was used to establish the diagnosis model of OA, which not only had excellent predictive power in internal and external data sets (AUC > 0.9), but also had high predictive performance in different chip platforms (AUC > 0.9) and also had effective ability in blood samples (AUC > 0.8). Conclusion: The 4-genes diagnostic model may be of great help to the early diagnosis and prediction of OA.

Download Full-text