FOXO and related transcription factors binding elements in the regulation of neurodegenerative disorders

Oli, Vaibhav; Gupta, Rohan; Kumar, Pravir

doi:10.1016/j.jchemneu.2021.102012

Cited by 21 publications

(9 citation statements)

References 160 publications

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“…As is known, ROS has been involved as a key factor in neurodegenerative disorders, such as AD and PD [ 38 , 39 ]. When ROS production exceeds the cellular clear capacity, oxidative stress occurs, resulting in oxidative injury and cell death.…”

Section: Discussionmentioning

confidence: 99%

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Wang

Gao

et al. 2022

Molecules

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Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB.

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Section: Discussionmentioning

confidence: 99%

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Wang

Gao

et al. 2022

Molecules

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“…FOXO3 belongs to the FOXO family, which regulates vital cellular processes including metabolism, proliferation, stress resistance, and apoptosis [56][57][58][59]. In C. elegans, the FOXOs transcription factor DAF-16 requires the β-catenin gene, bar-1, for longevity [60], suggesting β-catenin-FOXOs interaction might be pivotal for mammals' survival.…”

Section: Discussionmentioning

confidence: 99%

Tubular β-catenin alleviates mitochondrial dysfunction and cell death in acute kidney injury

Leung

Yiu

et al. 2022

Cell Death Dis

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Mitochondria take part in a network of intracellular processes that regulate homeostasis. Defects in mitochondrial function are key pathophysiological changes during AKI. Although Wnt/β-catenin signaling mediates mitochondrial dysfunction in chronic kidney fibrosis, little is known of the influence of β-catenin on mitochondrial function in AKI. To decipher this interaction, we generated an inducible mouse model of tubule-specific β-catenin overexpression (TubCat), and a model of tubule-specific β-catenin depletion (TubcatKO), and induced septic AKI in these mice with lipopolysaccharide (LPS) and aseptic AKI with bilateral ischemia-reperfusion. In both AKI models, tubular β-catenin stabilization in TubCat animals significantly reduced BUN/serum creatinine, tubular damage (NGAL-positive tubules), apoptosis (TUNEL-positive cells) and necroptosis (phosphorylation of MLKL and RIP3) through activating AKT phosphorylation and p53 suppression; enhanced mitochondrial biogenesis (increased PGC-1α and NRF1) and restored mitochondrial mass (increased TIM23) to re-establish mitochondrial homeostasis (increased fusion markers OPA1, MFN2, and decreased fission protein DRP1) through the FOXO3/PGC-1α signaling cascade. Conversely, kidney function loss and histological damage, tubular cell death, and mitochondrial dysfunction were all aggravated in TubCatKO mice. Mechanistically, β-catenin transfection maintained mitochondrial mass and activated PGC-1α via FOXO3 in LPS-exposed HK-2 cells. Collectively, these findings provide evidence that tubular β-catenin mitigates cell death and restores mitochondrial homeostasis in AKI through the common mechanisms associated with activation of AKT/p53 and FOXO3/PGC-1α signaling pathways.

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“… 61 Moreover, they can play a key role in the activation or inhibition of AD-related signaling pathways. 62 - 64 The KEGG results showed that the pathways of LDP in the treatment of AD were mainly enriched in the B cell receptor-signaling pathway and in HIV-1 and HCMV infections. Studies have shown that activated B cells can not only induce the differentiation of effector T cells and lead to neuroinflammation 65 - 67 but also participate in the pathological process of AD by secreting cytokines and acting on other immune cells (such as macrophages).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Approach for Exploring the Immune Cell Infiltration Patterns in Alzheimer’s Disease and Determining the Intervention Mechanism of Liuwei Dihuang Pill

et al. 2022

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Traditional Chinese medicine (TCM) compounds have recently garnered attention for the regulation of immune cell infiltration and the prevention and treatment of Alzheimer’s disease (AD). The Liuwei Dihuang Pill (LDP) has potential in this regard; however, its specific molecular mechanism currently remains unclear. Therefore, we adopted a bioinformatics approach to investigate the infiltration patterns of different types of immune cells in AD and explored the molecular mechanism of LDP intervention, with the aim of providing a new basis for improving the clinical immunotherapy of AD patients. We found that M1 macrophages showed significantly different degrees of infiltration between the hippocampal tissue samples of AD patients and healthy individuals. Four immune intersection targets of LDP in the treatment of AD were identified; they were enriched in 206 biological functions and 30 signaling pathways. Quercetin had the best docking effect with the core immune target PRKCB. Our findings suggest that infiltrated immune cells may influence the course of AD and that LDP can regulate immune cell infiltration through multi-component, multi-target, and multi-pathway approaches, providing a new research direction regarding AD immunotherapy.

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FOXO and related transcription factors binding elements in the regulation of neurodegenerative disorders

Cited by 21 publications

References 160 publications

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Tubular β-catenin alleviates mitochondrial dysfunction and cell death in acute kidney injury

Bioinformatics-Based Approach for Exploring the Immune Cell Infiltration Patterns in Alzheimer’s Disease and Determining the Intervention Mechanism of Liuwei Dihuang Pill

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