Implications of Phosphoinositide 3-Kinase-Akt (PI3K-Akt) Pathway in the Pathogenesis of Alzheimer’s Disease

Kumar, Manish; Bansal, Nitin

doi:10.1007/s12035-021-02611-7

Cited by 99 publications

(53 citation statements)

References 280 publications

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“…Our data showed that ROS reduced GLUT1 expression by suppressing PI3K/Akt pathway activity resulting in impaired glucose metabolism. The latest review summarized the role of PI3K/Akt pathway in AD and supported our results [28] . The article pointed out that abnormalities of the PI3K/Akt pathway, especially a decrease in Akt phosphorylation, prevented GLUT from transporting glucose into the cell and reduced ATP.…”

Section: Activated Pi3k/akt/glut1 Increased the Glucose Uptake And Atp Contents Decreased Aβ Levels In N2a/app695swe Cellssupporting

confidence: 81%

Scavenging ROS Decreases Amyloid-beta Levels via Activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe Cells

Peng

Zhang

Zhou

et al. 2021

Preprint

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Dysregulated glucose metabolism in the brain is considered to be the underlying cause of Alzheimer's disease (AD). Abnormal glucose metabolism in AD is associated with decreased glucose transporter 1 (GLUT1) and GLUT3 in the brain, but the underlying mechanisms remains unclear. Here, we reported that GLUT1 expression was decreased in N2a/APP695swe cells and GLUT3 expression was not significantly changed. Flow Cytometry analysis showed a significant increase of intracellular ROS content in N2a/APP695swe cells and GLUT1 expression was upregulated after treatment with the ROS scavenger N-acetyl-L-Cysteine (NAC). Cellular glucose uptake and ATP levels were reduced following decreased GLUT1 expression and increased after upregulating GLUT1. Western blot analyses showed that phosphorylation of PI3K/Akt pathway decreased in N2a/APP695swe cells. Aβ levels decreased after upregulation of GLUT1 expression and increased after downregulation of GLUT1. After NAC treatment, PI3K/Akt pathway phosphorylation levels and GLUT1 expression were upregulated, glucose uptake and ATP contents were increased, and Aβ levels were decreased. After adding PI3K/Akt pathway inhibitor LY29004, GLUT1 expression was reduced and Aβ levels were increased. Besides, the increased glucose uptake and ATP contents by the Akt activator SC79 were hindered with the GLUT1 inhibitor WZB117. Aβ levels decreased after SC79 treatment and increased after WZB117 treatment. Overall, our data suggest that ROS reduced GLUT1 expression by inhibiting PI3K/Akt pathway activity resulting in impaired glucose metabolism and scavenging ROS prevents Aβ via activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe cells.

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Section: Activated Pi3k/akt/glut1 Increased the Glucose Uptake And Atp Contents Decreased Aβ Levels In N2a/app695swe Cellssupporting

confidence: 81%

Scavenging ROS Decreases Amyloid-beta Levels via Activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe Cells

Peng

Zhang

Zhou

et al. 2021

Preprint

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“…Analysis of the abnormal upregulation of miR-484 in bipolar disorder exosomes using the Kyoto Gene and Genome Encyclopedia (KEGG) pathway with DIANA-miRPath v3.0 revealed that it was mainly associated with the PI3K/Akt signaling pathway ( 96 ) ( Table 2 ) . Interestingly, the PI3K-Akt signaling pathway may be an important target for AD therapy ( 97 ). In addition, it has been proposed that low levels of miR-484 are associated with rapid cognitive decline ( 67 ).…”

Section: The Role Of Mir-484 In Non-cancerous Diseasesmentioning

confidence: 99%

miR-484: A Potential Biomarker in Health and Disease

et al. 2022

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Disorders of miR-484 expression are observed in cancer, different diseases or pathological states. There is accumulating evidence that miR-484 plays an essential role in the development as well as the regression of different diseases, and miR-484 has been reported as a key regulator of common cancer and non-cancer diseases. The miR-484 targets that have effects on inflammation, apoptosis and mitochondrial function include SMAD7, Fis1, YAP1 and BCL2L13. For cancer, identified targets include VEGFB, VEGFR2, MAP2, MMP14, HNF1A, TUSC5 and KLF12. The effects of miR-484 on these targets have been documented separately. Moreover, miR-484 is typically described as an oncosuppressor, but this claim is simplistic and one-sided. This review will combine relevant basic and clinical studies to find that miR-484 promotes tumorigenesis and metastasis in liver, prostate and lung tissues. It will provide a basis for the possible mechanisms of miR-484 in early tumor diagnosis, prognosis determination, disease assessment, and as a potential therapeutic target for tumors.

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“…The PI3K/AKT signaling pathway is a carcinogenic pathway involved in a variety of physiological processes, including proliferation, apoptosis, differentiation, migration, and invasion (109). The aberrant activation of this pathway is closely associated with many aspects of cancer progression, including drug resistance (110,111).…”

Section: Long Non-coding Rnas Target Signaling Pathways In Gastric Cancer Drug Resistancementioning

confidence: 99%

Long Non-Coding RNA in Gastric Cancer: Mechanisms and Clinical Implications for Drug Resistance

Liu

Yü

et al. 2022

Front. Oncol.

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Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide, with high recurrence and mortality rate. Chemotherapy, including 5-fluorouracil (5-FU), adriamycin (ADR), vincristine (VCR), paclitaxel (PTX), and platinum drugs, remains one of the fundamental methods of GC treatment and has efficiently improved patients’ prognosis. However, most patients eventually develop resistance to chemotherapeutic agents, leading to the failure of clinical treatment and patients’ death. Recent studies suggest that long non-coding RNAs (lncRNAs) are involved in the drug resistance of GC by modulating the expression of drug resistance-related genes via sponging microRNAs (miRNAs). Moreover, lncRNAs also play crucial roles in GC drug resistance via a variety of mechanisms, such as the regulation of the oncogenic signaling pathways, inhibition of apoptosis, induction of autophagy, modulation of cancer stem cells (CSCs), and promotion of the epithelial-to-mesenchymal transition (EMT) process. Some of lncRNAs exhibit great potential as diagnostic and prognostic biomarkers, as well as therapeutic targets for GC patients. Therefore, understanding the role of lncRNAs and their mechanisms in GC drug resistance may provide us with novel insights for developing strategies for individual diagnosis and therapy. In this review, we summarize the recent findings on the mechanisms underlying GC drug resistance regulated by lncRNAs. We also discuss the potential clinical applications of lncRNAs as biomarkers and therapeutic targets in GC.

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Implications of Phosphoinositide 3-Kinase-Akt (PI3K-Akt) Pathway in the Pathogenesis of Alzheimer’s Disease

Cited by 99 publications

References 280 publications

Scavenging ROS Decreases Amyloid-beta Levels via Activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe Cells

Scavenging ROS Decreases Amyloid-beta Levels via Activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe Cells

miR-484: A Potential Biomarker in Health and Disease

Long Non-Coding RNA in Gastric Cancer: Mechanisms and Clinical Implications for Drug Resistance

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