scholarly journals Integrated Genomic Analysis Highlights the Impaired PI3K-Akt Signaling Pathway in Alzheimer’s Disease

2021 ◽  
Vol 12 (2) ◽  
pp. 2332-2339
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Meta Analysis ◽  
Temporal Cortex ◽  
Genomic Analysis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Underlying Mechanisms ◽  
Treatment And Diagnosis

Alzheimer’s disease (AD), a leading cause of dementia, remained incurable, despite many advances in our knowledge about AD pathogenesis, underlying mechanisms are poorly understood. Transcriptome analysis showed efficiency in exploring these mechanisms; however, data are generated at a higher pace than interpreted and are almost inconsistent. Therefore we performed this meta-analysis to extract new knowledge from existing data and find the mechanisms involved in AD. Five temporal cortex transcriptomics datasets from 187 AD patients and 167 healthy controls were analyzed. Our analysis showed that the PI3K-Akt signaling pathway is significantly impaired in AD brains and was common among all datasets. Moreover, miRs targeting genes involved in the PI3K-Akt signaling pathway were identified. In conclusion, our results highlight the impaired PI3K-Akt signaling pathway in AD and suggested related miRs as the potential targets for early treatment and diagnosis of AD.

scholarly journals Identifying mechanisms of Epimedii Folium against Alzheimer’s disease via a network pharmacology approach Epimedii Folium treats Alzheimer’s disease via PI3K-AKT

2021 ◽  
Vol 19 ◽  
pp. 205873922110414
Author(s):  
Yan Zhao ◽  
Guangmei Liu ◽  
Yang Yang ◽  
Ling Chen ◽  
Ying Shang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Target Therapy ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Pathway Gene

To elucidate the mechanism of the multi-target action of Epimedii Folium on Alzheimer’s disease, this study focuses on the analysis of network pharmacology. Based on a bioinformatics approach, this study obtained the effective components of Epimedium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, predicted the compound targets through the Pharmapper and Swiss target prediction database and then through Gene Expression Omnibus Datasets and Therapeutic Target Database. We collected and analysed of heral and disease targets, constructed the network. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology enrichment, then the key targets and pathways of Epimedii Folium to cope with Alzheimer’s disease have been identified. Twenty-three bioactive components and 477 potential target genes of Epimedii Folium were identified. A total of 1612 target diseases were identified. Through network module analysis, 30 hub target genes were identified. Through enrichment analysis of the KEGG pathway, hub target genes were largely enriched in the PI3K-AKT signaling pathway. Through the analysis of network pharmacology, it was found that Epimedii Folium might play the role of multi-compound and multi-target therapy through the PI3K-AKT signaling pathway. These findings provide helpful directions for future clinical studies.

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

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.

scholarly journals Cross–trait analysis of Alzheimer’s disease and gastrointestinal tract disorders identifies shared loci highlighting immune-related and statin pathways

2021 ◽  
Author(s):  
Emmanuel Adewuyi ◽  
Eleanor O’Brien ◽  
Dale Nyholt ◽  
Tenielle Porter ◽  
Simon Laws
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gastrointestinal Tract ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Ulcer Disease ◽  
Genome Wide ◽  
Underlying Mechanisms ◽  
Irritable Bowel

Abstract Several observational studies suggest a relationship between Alzheimer’s disease (AD) and gastrointestinal tract (GIT) disorders; however, their underlying mechanisms remain unclear. Here, we analysed several genome-wide association studies (GWAS) summary statistics (N = 34,652 – 456,327) to assess AD and GIT disorders relationships. We found a significant genetic overlap and correlation between AD and each of gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), medications for GERD or PUD (PGM), gastritis-duodenitis, irritable bowel syndrome and diverticulosis, but not inflammatory bowel disease. Our analysis suggests a partial causal association between AD and gastritis-duodenitis, diverticulosis and medication for PUD. GWAS meta-analysis identified seven loci (P < 5 × 10-8, PDE4B, CD46, SEMA3F, HLA-DRA, MTSS2, PHB, and APOE) shared by AD and PGM, six of which are novel. These loci were replicated using GERD and PUD GWAS and reinforced in gene-based analyses. Lipid metabolism, autoimmune system, lipase inhibitors, PD-1 signalling, and statin pathways were significantly enriched for AD and GIT disorders. These findings support shared genetic susceptibility in AD and GIT disorders. Lipase inhibitors and statins may provide novel therapeutic avenues for AD, GIT disorders, or their comorbidity.

scholarly journals ACSL1 Inhibits ALV-J Replication by IFN-Ⅰ Signaling and PI3K/Akt Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Qihong Zhang ◽  
Tingting Xie ◽  
Guodong Mo ◽  
Zihao Zhang ◽  
Ling Lin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Hematopoietic Malignancy ◽  
Interferon Stimulated Genes ◽  
Primary Monocyte ◽  
Chain Acyl ◽  
Underlying Mechanisms ◽  
Long Chain

J subgroup avian leukosis virus (ALV-J) infection causes serious immunosuppression problems, leading to hematopoietic malignancy tumors in chicken. It has been demonstrated that interferon-stimulated genes (ISGs) could limit ALV-J replication; nevertheless, the underlying mechanisms remain obscure. Here, we demonstrate that Long-chain Acyl-CoA synthetase 1 (ACSL1) is an interferon (IFN)-stimulated gene that specifically restricts the replication of ALV-J due to the higher IFN-I production. More importantly, ACSL1 induces primary monocyte-derived macrophages (MDMs) to pro-inflammatory phenotypic states during ALV-J infection, and ACSL1 mediates apoptosis through the PI3K/Akt signaling pathway in ALV-J-infected primary monocyte-derived macrophages (MDMs). Overall, these results provide evidence that ACSL1 contributes to the antiviral response against ALV-J.

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