Safinamide protects against amyloid β (Aβ)-induced oxidative stress and cellular senescence in M17 neuronal cells.
Safinamide protects against amyloid β (Aβ)-induced oxidative stress and cellular senescence in M17 neuronal cells.
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Safinamide 可防止 M17 神经元细胞中淀粉样蛋白 β (Aβ) 诱导的氧化应激和细胞衰老
DOI：
10.1080/21655979.2021.2022262
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发表时间：
2022-01
期刊：
影响因子：
4.9
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Gu X;Zhang G;Qin Z;Yin M;Chen W;Zhang Y;Liu X
阿尔茨海默病（Alzheimer's disease，AD）是一种与氧化应激和细胞衰老有关的神经退行性疾病。Safinamide是临床处方单胺氧化酶B（MAOB）抑制剂之一。据报道，它在神经系统疾病中具有治疗潜力。然而，沙非酰胺在AD中的治疗潜力仍在研究中。在这项研究中，我们探讨了沙非酰胺在淀粉样蛋白（Aβ）1-42寡聚体刺激的M17神经细胞中的作用。我们用1 μM Aβ1-42寡聚体（含或不含沙非酰胺（100或200 nM））处理M17细胞，建立了体外模型。结果表明，沙非酰胺改善了Aβ1-42寡聚体诱导的M17细胞氧化应激，表现为活性氧（ROS）产生减少和还原型谷胱甘肽（GSH）含量降低。Safinamide治疗显著改善衰老相关β-半乳糖苷酶（SA-β-gal）阳性细胞和端粒酶活性。此外，我们发现，沙非酰胺治疗导致p21和纤溶酶原激活物抑制剂-1（派-1）的mRNA和蛋白表达下降。沉默SIRT 1可阻断沙非酰胺对Aβ1-42寡聚体诱导的M17细胞中p21和派-1 mRNA水平以及SA-β-gal阳性细胞的影响。结论：沙非酰胺通过SIRT 1信号通路对Aβ1-42寡聚体诱导的M17细胞氧化应激和细胞衰老具有保护作用。这些结果为沙非酰胺可能用于预防和治疗AD提供了有意义的证据。
Alzheimer’s disease (AD) is a neurodegenerative disorder that is pathologically related to oxidative stress and cellular senescence. Safinamide is one of the clinically prescribed monoamine oxidase B (MAOB) inhibitors. It has been reported to possess therapeutic potential in neurological disorders. However, the therapeutic potential of safinamide in AD is still under investigation. In this study, we explored the effect of safinamide in amyloid (Aβ)1–42 oligomers-stimulated M17 neuronal cells. We established the in vitro model with M17 cells by treating them with 1 μM Aβ1-42 oligomers with or without safinamide (100 or 200 nM). The results show that safinamide ameliorated Aβ1-42 oligomers-induced oxidative stress in M17 cells as revealed by the decreased reactive oxygen species (ROS) production and reduced glutathione (GSH) content. Safinamide treatment significantly ameliorated senescence-associated-β-galactosidase (SA-β-gal)-positive cells and telomerase activity. Further, we show that safinamide treatment resulted in decreased mRNA and protein expressions of p21 and plasminogen activator inhibitor-1 (PAI-1). Moreover, silencing of Sirtuin1 (SIRT1) abolished the effects of safinamide on the mRNA levels of p21 and PAI-1, as well as SA-β-gal-positive cells in Aβ1-42 oligomers-induced M17 cells. In conclusion, we reveal that safinamide exerted a protective function on M17 cells from Aβ1-42 oligomers induction-caused oxidative stress and cellular senescence through SIRT1 signaling. These present results provide meaningful evidence that safinamide may be medically developed for the prevention and therapy of AD.
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影响因子：
3.6
作者：
Liguori I;Russo G;Curcio F;Bulli G;Aran L;Della-Morte D;Gargiulo G;Testa G;Cacciatore F;Bonaduce D;Abete P
通讯作者：
Abete P
DOI：
10.3233/jad-170732
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Mecocci P;Boccardi V;Cecchetti R;Bastiani P;Scamosci M;Ruggiero C;Baroni M
通讯作者：
Baroni M
影响因子：
11.4
作者：
Cheignon C;Tomas M;Bonnefont-Rousselot D;Faller P;Hureau C;Collin F
通讯作者：
Collin F
DOI：
10.3390/molecules25245789
发表时间：
2020-12-08
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Breijyeh Z;Karaman R
通讯作者：
Karaman R
DOI：
10.1007/978-1-4939-6670-7_3
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Shtutman M;Chang BD;Schools GP;Broude EV
通讯作者：
Broude EV