NDRG4 Alleviates Aβ1–40 Induction of SH-SY5Y Cell Injury via Activation of BDNF-Inducing Signalling Pathways

Tai, Kang; Qu, Qing; Xie, Zhen; Cao, Bingqing

doi:10.1007/s11064-020-03011-4

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…These were in turn found to be involved in triggering secondary signaling pathways through GRIN2B, which is associated with cocaine addiction, cognitive central hypoventilation syndrome and eating disorders. A number of research studies have reported downregulation of BDNF expression, which is in line with our findings (Kang et al 2020 ; Akhtar et al 2020 ).…”

Section: Discussionsupporting

confidence: 92%

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

2021

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Alzheimer’s disease (AD), a dreadful neurodegenerative disorder that affects cognitive and behavioral function in geriatric populations, is characterized by the presence of amyloid deposits and neurofibrillary tangles in brain regions. The International D World Alzheimer Report 2018 noted a global prevalence of 50 million AD cases and forecasted a threefold rise to 139 million by 2050. Although there exist numerous genetic association studies pertinent to AD in different ethnicities, critical genetic factors and signaling pathways underlying its pathogenesis remain ambiguous. This study was aimed to analyze the genetic data retrieved from 32 Gene Expression Omnibus datasets belonging to diverse ethnic cohorts in order to identify overlapping differentially expressed genes (DEGs). Stringent selection criteria were framed to shortlist appropriate datasets based on false discovery rate (FDR) p -value and log FC, and relevant details of upregulated and downregulated DEGs were retrieved. Among the 32 datasets, only six satisfied the selection criteria. The GEO2R tool was employed to retrieve significant DEGs. Nine common DEGs, i.e., SLC5A3 , BDNF , SST , SERPINA3 , RTN3 , RGS4 , NPTX , ENC1 and CRYM were found in more than 60% of the selected datasets. These DEGs were later subjected to protein–protein interaction analysis with 18 AD-specific literature-derived genes. Among the nine common DEGs, BDNF , SST , SERPINA3 , RTN3 and RGS4 exhibited significant interactions with crucial proteins including BACE1, GRIN2B, APP, APOE, COMT, PSEN1, INS, NEP and MAPT. Functional enrichment analysis revealed involvement of these genes in trans-synaptic signaling, chemical transmission, PI3K pathway signaling, receptor–ligand activity and G protein signaling. These processes are interlinked with AD pathways.

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Section: Discussionsupporting

confidence: 92%

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

2021

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“…Chromatographic analysis indicated that for purified PI3K, the IC50 of LY294002 was 1.4 μM [32]. However, in different cell models, its inhibitory concentration has been reported to range from 1 to 50 μM [33][34][35]. The concentration of LY294002 used in this study was 5 μM, and the experimental results also showed that p-Akt was still expressed in the LY294002 group, suggesting that this experiment only partially inhibited the PI3K/Akt pathway, and rhEPO exerted a protective effect through the remaining part of the PI3K/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway

et al. 2022

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Objective Previous studies have found that recombinant human erythropoietin (rhEPO) protects long-term cultured ageing primary nerve cells by enhancing the endogenous antioxidant capacity of cells; however, its signalling pathways are not clear. This study aimed to explore the relationship between the rhEPO and PI3K/Akt pathways in the protection of senescent nerve cells at the cellular level. Methods Primary nerve cells were cultured for 22 days to mimic the natural ageing process of nerve cells. rhEPO and LY294002 were administered as an intervention on the 11th day of culture. Western blot, immunochemistry, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide, immunofluorescence double-labelling staining, Annexin V-FITC/PI double-labelling flow cytometry, and SA-β-gal staining experiments were used to observe the expression levels of erythropoietin receptor (EPOR) and phosphorylated Akt (p-Akt) protein and the related indices of nerve cell senescence. Results Western blot experiments showed that in ageing long-term cultured primary neurons, the EPOR and p-Akt decreased and rhEPO upregulated the expression levels of EPOR and p-Akt protein. The rest showed that the PI3K/Akt pathway blockade reduced the antioxidation capacity, cell viability, cell morphology, and ratio of apoptotic cells and senescent cells of rhEPO on ageing long-term cultured primary nerve cells. Conclusions This study explored the relationship between the rhEPO and PI3K/Akt pathways in the protection of ageing nerve cells at the cellular level and found that rhEPO protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway. These findings provide a theoretical basis and experimental evidence for the antiaeging mechanism of EPO in the nervous system.

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The Neuroprotective Effect of GM-1 Ganglioside on the Amyloid-Beta-Induced Oxidative Stress in PC-12 Cells Mediated by Nrf-2/ARE Signaling Pathway

Wang

Li²,

Yu³

et al. 2022

Neurochem Res

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NDRG4 Alleviates Aβ1–40 Induction of SH-SY5Y Cell Injury via Activation of BDNF-Inducing Signalling Pathways

Cited by 5 publications

References 33 publications

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

Recombinant human erythropoietin protects long-term cultured ageing primary nerve cells by upregulating the PI3K/Akt pathway

The Neuroprotective Effect of GM-1 Ganglioside on the Amyloid-Beta-Induced Oxidative Stress in PC-12 Cells Mediated by Nrf-2/ARE Signaling Pathway

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