The Multiple Roles of Autophagy in Neural Function and Diseases

Li, Yan-Yan; Qin, Zheng-Hong; Sheng, Rui

doi:10.1007/s12264-023-01120-y

Cited by 23 publications

(7 citation statements)

References 232 publications

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“…Some other studies have found that oxygen-glucose deprivation can lead to autophagy in PC12 cells, and inhibition of autophagy can decrease the cell viability and aggravate the damage [26] . But studies have found that autophagy has dual character in determining the fate of damaged nerve cells: appropriate activation is bene cial to maintain the energy and the survival of cell homeostasis under the ischemic stress, while excessive or prolonged activation of autophagy can cause neuronal necrosis and apoptosis [27] . Microtubule-associated protein light chain (LC3) is one of the speci c components of autophagosome membrane, and is a speci c component of mammalian autophagosome membrane.…”

Section: Discussionmentioning

confidence: 99%

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Shi,

Gao,

Wang

et al. 2024

Preprint

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Objectives To evaluate the role of hypothermia in the injury of PC12 cells which induced by OGD/R. To investigate the mechanism of hypothermia intervention to alleviate OGD/R-induced injury of PC12 cells through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and autophagy, and to lay a foundation and provide theoretical basis for clinical application of hypothermia on protect nerve injury in the future. Methods Induce PC12 cells establish an Ischemia reperfusion injury model in vitro by OGD/R. Then, intervene PC12 cells with OGD/R and OGD/R treated with LY294002 inhibitor at 37℃, 32℃, 27℃. Valuate cell viability by CCK-8 assay, detect the phosphorylation levels of PI3K, AKT and mTOR proteins through western blotting, evaluate signaling pathway activation of PI3K/AKT/mTOR, detect protein expression of LC3I/II by immunofluorescence and western blotting, and observe the autophagosomes by fluoroscopic electron microscopy to evaluate autophagy. Detect apoptosis by flow cytometry, and evaluate the cell damage. Results Hypothermia treatment could effectively improve the cell viability of PC12 cells treated with OGD/R, and the cell viability increased with the decrease of temperature (P < 0.05). Hypothermia treatment also promoted the increase of the phosphorylation levels of PI3K, AKT and mTOR proteins in cells (P < 0.05). In addition, flow cytometry was used to detect the apoptosis rate of different treatments, and the results showed that hypothermia could inhibit the apoptosis that induced by OGD/R. In the control group, OGD/R group and LY294002 inhibitor group, autophagy specific protein LC3I/II which labeled with green fluorescently was increased significantly under the culture conditions of 32℃ and 27℃, and the fluorescence signal was enhanced. Meanwhile, the expression level of LC3I/II also increased. Autophagosome was increased under the electron microscopy. Conclusion Hypothermia can inhibit apoptosis by regulating the PI3K/AKT/mTOR axis and the level of autophagy, thus protecting PC12 cell damage that induced by OGD/R.

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Section: Discussionmentioning

confidence: 99%

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Shi,

Gao,

Wang

et al. 2024

Preprint

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“…The results showed that autophagy and other pathways are involved in the progression of AD. Autophagy is a process of cellular self-degradation, through which cells are able to clear or recover damaged or excess components from within, in order to maintain the stability of the cellular environment ( Li et al, 2023 ). One study suggested that autophagy reduces abnormal levels of β Starch-like protein deposition in the brain.…”

Section: Discussionmentioning

confidence: 99%

Genetic markers associated with ferroptosis in Alzheimer’s disease

Sun,

Xiao,

Tang

et al. 2024

Front. Aging Neurosci.

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ObjectiveFerroptosis is implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and vascular dementia, implying that it may have a regulatory effect on the progression of these diseases. However, the specific role of ferroptosis-related genes (FRGs) in Alzheimer’s disease (AD) is not yet fully understood. The aim of the study was to detect ferroptosis related genes with regulatory functions in the disease and explore potential mechanisms in AD.MethodsHub FRGs were obtained through multiple algorithms based on the GSE5281 dataset. The screening process was implemented by R packages including limma, WGCNA, glm and SVM-RFE. Gene Ontology classification and pathway enrichment analysis were performed based on FRGs. Biological processes involved with hub FRGs were investigated through GSVA and GSEA methods. Immune infiltration analysis was performed by the R package CIBERSORT. Receiver operating characteristic curve (ROC) was utilized to validate the accuracy of hub FRGs. The CeRNA network attempted to find non-coding RNA transcripts which may play a role in disease progression.ResultsDDIT4, MUC1, KLHL24, CD44, and RB1 were identified as hub FRGs. As later revealed by enrichment analysis, the hub FRGs had important effects on AD through involvement in diverse AD pathogenesis-related pathways such as autophagy and glutathione metabolism. The immune microenvironment in AD shows increased numbers of resting NK cells, macrophages, and mast cells, with decreased levels of CD8 T cells when compared to healthy samples. Regulatory T cells were positively correlated with MUC1, KLHL24, and DDIT4 expression, while RB1 showed negative correlations with eosinophils and CD8 T cells, suggesting potential roles in modulating the immune environment in AD.ConclusionOur research has identified five hub FRGs in AD. We concluded that ferroptosis may be involved in the disease.

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“…Five novel SHS-PC2 loci were mapped to 97 genes (nine genes in four loci mapped by all methods). Of these, SEMA3D encodes a member of the class III semaphorins that are involved in axon guidance during neuronal development 28 (two more class III semaphorins at this locus, SEMA3A and SEMA3E, also mapped by CI); DRAM1 is a regulator of autophagy in the context of mitochondrial dysfunction, implicated in neurodegeneration 29 ; MAPK8IP3 is another MAPK/ERK gene essential for the function and maintenance of neurons, with links to neurodevelopmental disorders 30 ; FCHO1 is involved in clathrin-coat assembly and clathrin-mediated endocytosis and has been implicated in immune deficiency 31,32 . Three novel SHS-PC3 loci were mapped to 62 genes, with five genes in three loci mapped by all four methods.…”

Section: Implicated Genesmentioning

confidence: 99%

Genome-wide association analysis of composite sleep health scores in 413,904 individuals

Goodman,

Faquih,

Paz

et al. 2024

Preprint

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Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, and together may provide a more complete picture of sleep health, while also illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p<8.3e-9), along with 341 previously reported loci (p<5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2=0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections to behavioral, psychological, and cardiometabolic traits.

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The Multiple Roles of Autophagy in Neural Function and Diseases

Cited by 23 publications

References 232 publications

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Genetic markers associated with ferroptosis in Alzheimer’s disease

Genome-wide association analysis of composite sleep health scores in 413,904 individuals

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