Metformin inhibits Aβ<sub>25‐35</sub>‐induced apoptotic cell death in SH‐SY5Y cells

Li, Lixia; Liu, Mengyu; Jiang, Xue; Xia, Zhenzhen; Wang, Yuxiang; An, Di; Wang, Honggang; Heng, Bin; Liu, Yanqiang

doi:10.1111/bcpt.13279

Cited by 20 publications

(27 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Metformin decreases the apoptosis of Aβ-treated SH-SY5Y neuroblastoma cells by repressing the intracellular concentration of Ca 2+ and ROS generation. Moreover, metformin enhances the autophagy process by promoting the conversion of microtubule-associated protein 1 light chain 3 (LC3) in neuroblastoma cells (Li et al, 2019). Underexposure to Aβ, the primary cultured rat hippocampal neurons have substantial neuronal death.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Metformin: A Novel Weapon Against Inflammation

Bai

Chen

2021

Front. Pharmacol.

View full text Add to dashboard Cite

It has become widely accepted that inflammation is a driving force behind a variety of chronic diseases, such as cardiovascular disease, diabetes, kidney disease, cancer, neurodegenerative disorders, etc. However, the existing nonsteroidal anti-inflammatory drugs show a limited utility in clinical patients. Therefore, the novel agents with different inflammation-inhibitory mechanisms are worth pursuing. Metformin, a synthetic derivative of guanidine, has a history of more than 50 years of clinical experience in treating patients with type 2 diabetes. Intense research efforts have been dedicated to proving metformin’s inflammation-inhibitory effects in cells, animal models, patient records, and randomized clinical trials. The emerging evidence also indicates its therapeutic potential in clinical domains other than type 2 diabetes. Herein, this article appraises current pre-clinical and clinical findings, emphasizing metformin’s anti-inflammatory properties under individual pathophysiological scenarios. In summary, the anti-inflammatory effects of metformin are evident in pre-clinical models. By comparison, there are still clinical perplexities to be addressed in repurposing metformin to inflammation-driven chronic diseases. Future randomized controlled trials, incorporating better stratification/targeting, would establish metformin’s utility in this clinical setting.

show abstract

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Metformin: A Novel Weapon Against Inflammation

Bai

Chen

2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…The present findings suggest that miR-33 interference strikingly inhibits activation of the Akt/mTOR signal pathway and upregulates autophagy. Oxidative stress, inflammation, and the endogenous caspase apoptosis pathway have been implicated in Ab neurotoxicity [6,26]. In this study, we uncovered the role of miR-33 in apoptosis, inflammation, and oxidative stress of neurons.…”

Section: Discussionmentioning

confidence: 91%

“…It has been reported that aggregated and accumulated Ab peptides can bring about hyperphosphorylation of tau protein and neurofibrillary tangles [5]. Evidence suggests that multiple factors, including apoptosis, inflammation, and oxidative stress, contribute to AD [6].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-33 Has Protective Effect Against Aβ₂₅₋₃₅-Induced Injury in SH-SH-SY5Y Cells

Wang

Huang

et al. 2020

Med Sci Monit

View full text Add to dashboard Cite

Background: Alzheimer disease (AD) is a significant health issue for the elderly, and there are at present no clinically effective anti-AD agents. Prevention of Ab-induced neurotoxicity is proposed as a possible modality for treatment of AD. miR-33 has been proven to promote Ab secretion and impair Ab clearance in neural cells. The present study assessed whether miR-33 is involved in AD pathology. Material/Methods: miR-33 level was detected by qRT-PCR. The Akt/mTOR pathway was analyzed by Western blot analysis. Neuron inflammation and oxidative stress were measured using commercial detection kits. Flow cytometry and Western blot assay were conducted to assess cell apoptosis, and Western blot assay was used to assess synaptic protein levels. Results: miR-33 expression level was markedly upregulated in SH-SY5Y cells treated with Ab 25-35. miR-33 knockdown suppressed inflammation, oxidative stress, and cell apoptosis. In addition, miR-33 knockdown improved synaptic plasticity, and the protective effect of miR-33 knockdown was discovered through suppressing activation of the Akt/mTOR signaling pathway. Conclusions: Taken together, these findings suggest that miR-33 knockdown protects against Ab 25-35-induced inflammation, oxidative stress, apoptosis, and synaptic damage by suppressing activation of the Akt/mTOR pathway.

show abstract

“…Previous studies have reported the cell toxicity of Aβ 25-35 peptide (10–30 µM) in PC12 and SH-SY5Y cells ( 30 – 32 ). Our previous study demonstrated that treatment with Aβ 25-35 peptide (10–30 µM) alone reduced the cell viability at 24, 48 and 72 h ( 22 ).…”

Section: Resultsmentioning

confidence: 99%

Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells

Wang,

Li,

et al. 2023

Mol Med Rep

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the most common type of age-related dementia, and causes progressive memory degradation, neuronal loss and brain atrophy. The pathological hallmarks of AD consist of amyloid-β (Aβ) plaque accumulation and abnormal neurofibrillary tangles. Amyloid fibrils are constructed from Aβ peptides, which are recognized to assemble into toxic oligomers and exert cytotoxicity. The fibrillar Aβ-protein fragment 25–35 (Aβ 25-35 ) induces local inflammation, thereby exacerbating neuronal apoptosis. Notoginsenoside R1 (NGR1), one of the primary bioactive ingredients isolated from Panax notoginseng , exhibits effective anti-inflammatory and anti-oxidative activities. However, NGR1 pharmacotherapies targeting Aβ-induced inflammation and cell injury cascade remain to be elucidated. The present study investigated the effect and mechanism of NGR1 in Aβ 25-35 -treated PC12 cells. NGR1 doses between 250 and 1,000 µg/ml significantly increased cell viability suppressed by 20 µM Aβ 25-35 peptide treatment. Notably, the present study demonstrated that Aβ 25-35 peptide-induced sphingosine kinase 1 (SphK1) signaling activation was reduced after NGR1 treatment, further inhibiting the downstream NF-κB inflammatory signaling pathway. In addition, administration of SphK1 inhibitor II (SKI–II), a SphK1 inhibitor, also significantly reduced Aβ 25-35 peptide-induced apoptosis and the ratio of NF-κB p-p65/p65. Furthermore, SphK1 knockdown in PC12 cells using small interfering RNA alleviated Aβ-induced cell apoptosis and inflammation, suggesting a pivotal role of SphK1 signaling in the anti-inflammatory effect of NGR1. In summary, NGR1 alleviated inflammation and apoptosis stimulated by Aβ 25-35 by inhibiting the SphK1/NF-κB signaling pathway and may be a promising agent for future AD treatment.

show abstract

Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells

Cited by 20 publications

References 58 publications

Metformin: A Novel Weapon Against Inflammation

Metformin: A Novel Weapon Against Inflammation

Downregulation of miR-33 Has Protective Effect Against Aβ₂₅₋₃₅-Induced Injury in SH-SH-SY5Y Cells

Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells

Contact Info

Product

Resources

About

Metformin inhibits Aβ25‐35‐induced apoptotic cell death in SH‐SY5Y cells

Cited by 20 publications

References 58 publications

Metformin: A Novel Weapon Against Inflammation

Metformin: A Novel Weapon Against Inflammation

Downregulation of miR-33 Has Protective Effect Against Aβ₂₅₋₃₅-Induced Injury in SH-SH-SY5Y Cells

Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells

Contact Info

Product

Resources

About

Metformin inhibits Aβ_25‐35‐induced apoptotic cell death in SH‐SY5Y cells