Integrated analysis and network pharmacology approaches to explore key genes of Xingnaojing for treatment of Alzheimer's disease

Wang, Meixia; Wang, Shouyong; Li, Yong; Cai, Gaomei; Cao, Min; Li, Lanfang

doi:10.1002/brb3.1610

Cited by 12 publications

(9 citation statements)

References 29 publications

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“…Ten hub genes were identified, including SNAP25, ENO2, ELAVL4, GAP43, SNAP91, SYP, BSN, NEFM, and NEFL (Figures 4A,B). Among them, six genes (SNAP25, KIF1A, GAP43, BSN, SYP, and NEFL) have been widely investigated in AD in previous studies (Tien et al, 2011;Agostini et al, 2019;Jia et al, 2020;Ren et al, 2020;Wang M. et al, 2020). Therefore, we selected the remaining four hub genes (ENO2, ELAVL4, SNAP91, and NEFM) to analyze their role in AD.…”

Section: Selection Of Hub Genes From Trait-related Genes Using Proteimentioning

confidence: 99%

Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis

Hu¹,

Zhou³

et al. 2020

Front. Aging Neurosci.

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Background: The pathogenesis of Alzheimer’s disease (AD) remains to be elucidated. This study aimed to identify the hub genes in AD pathogenesis and determine their functions and pathways.Methods: A co-expression network for an AD gene dataset with 401 samples was constructed, and the AD status-related genes were screened. The hub genes of the network were identified and validated by an independent cohort. The functional pathways of hub genes were analyzed.Results: The co-expression network revealed a module that related to the AD status, and 101 status-related genes were screened from the trait-related module. Gene enrichment analysis indicated that these status-related genes are involved in synaptic processes and pathways. Four hub genes (ENO2, ELAVL4, SNAP91, and NEFM) were identified from the module, and these hub genes all participated in AD-related pathways, but the associations of each gene with clinical features were variable. An independent dataset confirmed the different expression of hub genes between AD and controls.Conclusions: Four novel genes associated with AD pathogenesis were identified and validated, which provided novel therapeutic targets for AD.

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Section: Selection Of Hub Genes From Trait-related Genes Using Proteimentioning

confidence: 99%

Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis

Hu¹,

Zhou³

et al. 2020

Front. Aging Neurosci.

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“…52,53 Previous studies using candidate gene designs have provided tentative evidence that genetic variation in SORCS3 may be associated with AD. 52,53 I n a recent GWAS of dementia in women enrolled in the the Women’s Health Initiative, 54 a SORCS3 intronic rare variant, rs76590698, was significantly associated with dementia ( p = 2×10−8. 55 In the GWAS Catalog, SORCS3 -mapped variants are significantly associated with multiple cognitively relevant phenotypes, including depressive symptoms (rs1021363, p = 1×10−13), self-reported educational attainment (rs11599236, p = 1×10−13), and systolic blood pressure (rs191784289, p = 3×10−13).…”

Section: Discussionmentioning

confidence: 99%

“…SORCS3 codes for the sortilin-related VPS10 domain-containing receptor 3, a vacuolar protein expressed in the brain (see Supplementary Figure S1 for gene interaction network). 52,53 Previous studies using candidate gene designs have provided tentative evidence that genetic variation in SORCS3 may be associated with AD. 52,53 I n a recent GWAS of dementia in women enrolled in the the Women’s Health Initiative, 54 a SORCS3 intronic rare variant, rs76590698, was significantly associated with dementia ( p = 2×10−8.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of brain arteriolosclerosis

Shade

Katsumata

Hohman

et al. 2022

J Cereb Blood Flow Metab

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Brain arteriolosclerosis (B-ASC) is characterized by pathologically altered brain parenchymal arterioles. B-ASC is associated with cognitive impairment and increased likelihood of clinical dementia. To date, no study has been conducted on genome-wide genetic risk of autopsy-proven B-ASC. We performed a genome-wide association study (GWAS) of the B-ASC phenotype using multiple independent aged neuropathologic cohorts. Included in the study were participants with B-ASC autopsy and genotype data available from the NACC, ROSMAP, ADNI, and ACT data sets. Initial Stage 1 GWAS ( n = 3382) and Stage 2 mega-analysis ( n = 4569) were performed using data from the two largest cohorts (NACC and ROSMAP). Replication of top variants and additional Stage 3 mega-analysis were performed incorporating two smaller cohorts (ADNI and ACT). Lead variants in the top two loci in the Stage 2 mega-analysis (rs7902929, p = [Formula: see text]; rs2603462, p = [Formula: see text]) were significant in the ADNI cohort (rs7902929, p = [Formula: see text]; rs2603462, p = [Formula: see text]). The rs2603462 lead variant colocalized with ELOVL4 expression in the cerebellum (posterior probability = 90.1%). Suggestive associations were also found near SORCS1 and SORCS3. We thus identified putative loci associated with B-ASC risk, but additional replication is needed.

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“…There was also a small number of genes (n = 9) that were downregulated early, but were even further diminished at the two-week time point including Adra2a, Ccdc33, Dpp10, Fdft1, Hmcn1, Klhl14, Slc38a4, Tacr3, and Tfrc. Each of these genes have been reported as downregulated in models of chronic neurodegenerative disease such as Alzheimer's and Parkinson's 41,42,51,52,[43][44][45][46][47][48][49][50] .…”

Section: Enrichment For Apoptosis Terms Was Highly Significant In Acutely Upregulated Genesmentioning

confidence: 99%

Transcriptional Pathology Evolves Over Time in Rat Hippocampus Following Lateral Fluid Percussion Traumatic Brain Injury

Catta-Preta

Zdillar

Jenner

et al. 2021

Preprint

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Traumatic brain injury (TBI) causes acute and lasting impacts on the brain, driving pathology along anatomical, cellular, and behavioral dimensions. Rodent models offer the opportunity to study TBI in a controlled setting, and enable analysis of the temporal progression that occurs from injury to recovery. We applied transcriptomic and epigenomic analysis, characterize gene expression and in ipsilateral hippocampus at 1 and 14 days following moderate lateral fluid percussion (LFP) injury. This approach enabled us to identify differential gene expression (DEG) modules with distinct expression trajectories across the two time points. The major DEG modules represented genes that were up- or downregulated acutely, but largely recovered by 14 days. As expected, DEG modules with acute upregulation were associated with cell death and astrocytosis. Interestingly, acutely downregulated DEGs related to neurotransmission mostly recovered by two weeks. Upregulated DEG modules related to inflammation were not necessarily elevated acutely, but were strongly upregulated after two weeks. We identified a smaller DEG module with delayed downregulation at 14 days including genes related to cholesterol metabolism and amyloid beta clearance. Finally, differential expression was paralleled by changes in H3K4me3 at the promoters of differentially expressed genes at one day following TBI. Following TBI, changes in cell viability, function and ultimately behavior are dynamic processes. Our results show how transcriptomics in the preclinical setting has the potential to identify biomarkers for injury severity and/or recovery, to identify potential therapeutic targets, and, in the future, to evaluate efficacy of an intervention beyond measures of cell death or spatial learning.

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Integrated analysis and network pharmacology approaches to explore key genes of Xingnaojing for treatment of Alzheimer's disease

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 12 publications

References 29 publications

Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis

Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis

Genome-wide association study of brain arteriolosclerosis

Transcriptional Pathology Evolves Over Time in Rat Hippocampus Following Lateral Fluid Percussion Traumatic Brain Injury

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