Re-exploring the core genes and modules in the human frontal cortex during chronological aging: insights from network-based analysis of transcriptomic studies

Xu, Mulin; Liu, Yu; Huang, Yi; Wang, Jinli; Yan, Jinhua; Zhang, Le; Zhang, Cuntai

doi:10.18632/aging.101589

Cited by 6 publications

(2 citation statements)

References 48 publications

(42 reference statements)

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“…Specific functions of the downregulated proteins are provided in Table S3. ,− Biological functions of downregulated proteins consist of trafficking and cell morphology (AHSG, AP2A2, COL1A2, COL4A2, DCN, FAT1, KIF5B, LLGL1, NID1, NUMA1, SEPT2, and TPM4) biochemical and binding activities (ALDOA, ANXA5, ASS1, ATP1A2, CKB, CLIC1, LOXL3, PLOD1, PSAP, PYGB, SLC9A3R1, and SPOCK1), synaptic regulation (CTTNNA2 and SPON1), chaperone protein folding (HSP90B1 and HSPD1), development and growth (CTTNNA2, SPON1, and YES1), transcriptional nuclear regulation (PARP1, SSBP1, and XRCC5), and cell signaling ...…”

Section: Resultsmentioning

confidence: 99%

Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons

et al. 2021

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The accumulation and propagation of hyperphosphorylated tau (p-Tau) is a neuropathological hallmark occurring with neurodegeneration of Alzheimer’s disease (AD). Extracellular vesicles, exosomes, have been shown to initiate tau propagation in the brain. Notably, exosomes from human-induced pluripotent stem cell (iPSC) neurons expressing the AD familial A246E mutant form of presenilin 1 (mPS1) are capable of inducing tau deposits in the mouse brain after in vivo injection. To gain insights into the exosome proteome cargo that participates in propagating tau pathology, this study conducted proteomic analysis of exosomes produced by human iPSC neurons expressing A246E mPS1. Significantly, mPS1 altered the profile of exosome cargo proteins to result in (1) proteins present only in mPS1 exosomes and not in controls, (2) the absence of proteins in the mPS1 exosomes which were present only in controls, and (3) shared proteins which were upregulated or downregulated in the mPS1 exosomes compared to controls. These results show that mPS1 dysregulates the proteome cargo of exosomes to result in the acquisition of proteins involved in the extracellular matrix and protease functions, deletion of proteins involved in RNA and protein translation systems along with proteasome and related functions, combined with the upregulation and downregulation of shared proteins, including the upregulation of amyloid precursor protein. Notably, mPS1 neuron-derived exosomes displayed altered profiles of protein phosphatases and kinases involved in regulating the status of p-tau. The dysregulation of exosome cargo proteins by mPS1 may be associated with the ability of mPS1 neuron-derived exosomes to propagate tau pathology.

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Section: Resultsmentioning

confidence: 99%

Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons

et al. 2021

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“…We selected GSE48350 database, which contains microarray data from AD cases (aged 20–99 years) and age matched normal controls, from 4 brain regions: hippocampus, entorhinal cortex, superior frontal cortex, and post-central gyrus. Previous study has demonstrated that frontal cortical dysfunction contributed a significant extent to cognitive deficits and memory loss, which was considered as the late characteristic of AD [53]; meanwhile, AD has been widely considered as an early amnesic syndrome of hippocampal type, which on behalf of the most significant clinic feature for the diagnosis of AD [54–56], and we believed that the data between age-matched AD patients and normal controls were more convictive. Besides, entorhinal cortex is also considered as a vital brain region in characterizing AD, and aberrant changes of entorhinal cortex happen before hippocampus in the pathological mechanism of AD [57–59].…”

Section: Discussionmentioning

confidence: 99%

Integrated identification of key genes and pathways in Alzheimer’s disease via comprehensive bioinformatical analyses

2019

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Background Alzheimer’s disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete. Methods Gene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cortex regions between AD patients and healthy controls and detected via Morpheus. Functional enrichment analyses, including Gene Ontology (GO) and pathway analyses of DEGs, were performed via Cytoscape and followed by the construction of protein-protein interaction (PPI) network. Hub proteins were screened using the criteria: nodes degree≥10 (for hippocampus tissues) and ≥ 8 (for entorhinal cortex tissues). Molecular Complex Detection (MCODE) was used to filtrate the important clusters. University of California Santa Cruz (UCSC) and the database of RNA-binding protein specificities (RBPDB) were employed to identify the RNA-binding proteins of the long non-coding RNA (lncRNA). Results 251 & 74 genes were identified as DEGs, which consisted of 56 & 16 up-regulated genes and 195 & 58 down-regulated genes in hippocampus and entorhinal cortex, respectively. Biological analyses demonstrated that the biological processes and pathways related to memory, transmembrane transport, synaptic transmission, neuron survival, drug metabolism, ion homeostasis and signal transduction were enriched in these genes. 11 genes were identified as hub genes in hippocampus and entorhinal cortex, and 3 hub genes were identified as the novel candidates involved in the pathology of AD. Furthermore, 3 lncRNAs were filtrated, whose binding proteins were closely associated with AD. Conclusions Through GO enrichment analyses, pathway analyses and PPI analyses, we showed a comprehensive interpretation of the pathogenesis of AD at a systematic biology level, and 3 novel candidate genes and 3 lncRNAs were identified as novel and potential candidates participating in the pathology of AD. The results of this study could supply integrated insights for understanding the pathogenic mechanism underlying AD and potential novel therapeutic targets. Electronic supplementary material The online version of this article (10.1186/s41065-019-0101-0) contains supplementary material, which is available to authorized users.

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Re-exploring the core genes and modules in the human frontal cortex during chronological aging: insights from network-based analysis of transcriptomic studies

Cited by 6 publications

References 48 publications

Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons

Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons

Integrated identification of key genes and pathways in Alzheimer’s disease via comprehensive bioinformatical analyses

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