Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment
Aging-US ( IF 3.9 ) Pub Date : 2020-12-29 , DOI: 10.18632/aging.202453 Xiaohong Chen 1, 2 , João A. Amorim 3 , Giannis A. Moustafa 1 , Jong-Jer Lee 1 , Zhen Yu 1 , Kenji Ishihara 1 , Yasuhiro Iesato 1 , Paulo Barbisan 1 , Takashi Ueta 1 , Konstantina A. Togka 1 , Lin Lu 2 , David A. Sinclair 3 , Demetrios G. Vavvas 1, 4
Aging-US ( IF 3.9 ) Pub Date : 2020-12-29 , DOI: 10.18632/aging.202453 Xiaohong Chen 1, 2 , João A. Amorim 3 , Giannis A. Moustafa 1 , Jong-Jer Lee 1 , Zhen Yu 1 , Kenji Ishihara 1 , Yasuhiro Iesato 1 , Paulo Barbisan 1 , Takashi Ueta 1 , Konstantina A. Togka 1 , Lin Lu 2 , David A. Sinclair 3 , Demetrios G. Vavvas 1, 4
Affiliation
Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL+ photoreceptors, CD11b+ macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD+ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic in vitro studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.
中文翻译:
烟酰胺光变性视网膜脱离模型中烟酰胺单核苷酸(NMN)的神经保护作用和作用机制
目前,没有药物疗法被证明可有效治疗患者的感光细胞变性。因此,人们迫切需要发现容易获得且安全的神经保护剂。在这里,我们在视网膜脱离(RD)引起的感光细胞变性中研究了烟酰胺单核苷酸(NMN)(烟酰胺腺嘌呤二核苷酸(NAD +)的前体)。RD后NMN给药导致TUNEL +感光细胞,CD11b +巨噬细胞和GFAP标记的神经胶质细胞活化显着降低;蛋白质羰基含量(PCC)的标准化,以及外核层(ONL)厚度的保留。NMN管理显着增加了NAD +水平,SIRT1蛋白表达和血红素加氧酶1(HO-1)表达。RD后NMN延迟给药仍然发挥保护作用。使用661W细胞进行的体外机制研究显示,SIRT1 / HO-1信号作为NMN介导的氧化应激和LPS刺激保护的下游效应子。总之,NMN给药对RD和氧化损伤后的感光细胞具有神经保护作用,为治疗感光细胞变性提供了治疗途径。
更新日期:2021-01-01
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
烟酰胺光变性视网膜脱离模型中烟酰胺单核苷酸(NMN)的神经保护作用和作用机制
目前,没有药物疗法被证明可有效治疗患者的感光细胞变性。因此,人们迫切需要发现容易获得且安全的神经保护剂。在这里,我们在视网膜脱离(RD)引起的感光细胞变性中研究了烟酰胺单核苷酸(NMN)(烟酰胺腺嘌呤二核苷酸(NAD +)的前体)。RD后NMN给药导致TUNEL +感光细胞,CD11b +巨噬细胞和GFAP标记的神经胶质细胞活化显着降低;蛋白质羰基含量(PCC)的标准化,以及外核层(ONL)厚度的保留。NMN管理显着增加了NAD +水平,SIRT1蛋白表达和血红素加氧酶1(HO-1)表达。RD后NMN延迟给药仍然发挥保护作用。使用661W细胞进行的体外机制研究显示,SIRT1 / HO-1信号作为NMN介导的氧化应激和LPS刺激保护的下游效应子。总之,NMN给药对RD和氧化损伤后的感光细胞具有神经保护作用,为治疗感光细胞变性提供了治疗途径。