ArticleMolecular neurobiology2017
Hyperglycemia-Induced Oxidative-Nitrosative Stress Induces Inflammation and Neurodegeneration via Augmented Tuberous Sclerosis Complex-2 (TSC-2) Activation in Neuronal Cells.
Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
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- Jaranol alleviates cognitive impairment in db/db mice through the PI3K/AKT pathway.Metabolic brain disease · 2025Article
- A review of type 2 diabetes mellitus and cognitive impairment.Frontiers in endocrinology · 2025Review
- Analyzing the correlation between acute ischemic stroke and triglyceride-glucose index based on ordered logistic regression.Frontiers in neurology · 2025Article
- Association of preoperative blood glucose level with delirium after non-cardiac surgery in diabetic patients.Korean journal of anesthesiology · 2024Review
- Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies.Current medicinal chemistry · 2024Review
- Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes.Cell death & disease · 2023Article
- Effect of eIF2α in Neuronal Injury Induced by High Glucose and the Protective Mechanism of Resveratrol.Molecular neurobiology · 2023Article
- Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Cognitive dysfunction in diabetes: abnormal glucose metabolic regulation in the brain.Frontiers in endocrinology · 2023Review
- DNA Damage Response-Associated Cell Cycle Re-Entry and Neuronal Senescence in Brain Aging and Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Impaired fasting glucose, oxidative distress, and cognitive impairment. Is this the starting point on DBT cognitive decline?Frontiers in aging neuroscience · 2022Review
- Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression.Signal transduction and targeted therapy · 2021Review
- Increased levels of YKL-40 in patients with diabetes mellitus: a systematic review and meta-analysis.Diabetology & metabolic syndrome · 2021Article
- Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis.Cell death and differentiation · 2021Article
- Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain.Frontiers in genetics · 2021Article
- MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose.Clinical interventions in aging · 2021Article
- Unsupervised clustering of multiparametric fluorescent images extends the spectrum of detectable cell membrane phases with sub-micrometric resolution.Biomedical optics express · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes is a systemic disease mainly characterized by chronic hyperglycemia and with extensive and long-lasting spiteful complications in central nervous systems (CNS). Astrocytes play an important role in the defense mechanism of CNS, with great ability of withstanding accumulation of toxic substances. Apart from functional disorders, hyperglycemia leads to slow progressive structural abnormalities in the CNS through oxidative stress pathways. However, the molecular mechanism by which neurons die under oxidative stress induced by high glucose (HG) remains largely unclear. Here, we report that HG-induced inflammation and neurodegeneration in brain tissues, brain astrocytes (C6), and pheochromocytoma (PC-12) cells are cultured in HG conditions. Our results show that the increases in phosphorylation of Akt and ERK1/2MAPK are associated with increased accumulations of reactive oxygen species (ROS) in neuronal cells, which simultaneously enhanced phosphorylations of tuberous sclerosis complex-2 (TSC-2) and mammalian target of rapamycin (mTOR) in the diabetic brain and in HG-exposed neuronal cells. Pharmacologic inhibition of Akt or ERK1/2 or siRNA-mediated gene silencing of TSC-2 suppressed the strong downregulation of TSC-2-mTOR activation. Findings of this study also demonstrate that HG resulted in phosphorylation of NF-κB, coinciding with the increased production of inflammatory mediators and activation of neurodegenerative markers. Pretreatment of cells with antioxidants, phosphoinositide3-kinase (PI3-K)/Akt, and ERK1/2 inhibitors significantly reduced HG-induced TSC-2 phosphorylation and restored NF-κB protein expression leading to decreased production of inflammatory mediators and neurodegenerative markers. These results illustrate that ROS functions as a key signaling component in the regulatory pathway induced by elevated glucose in neuronal cell activation leading to inflammation and neurodegeneration.
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