针对聚胺氧化酶防止Excitotoxicity-Induced视网膜神经退化。

文章的细节

引用

徐Pichavaram P,蒂CD, Patel C, Z, E,综合商社Fouda AY,考德威尔RB, Narayanan SP

针对聚胺氧化酶防止Excitotoxicity-Induced视网膜神经退化。

前> 2019 1月10;12:956。doi: 10.3389 / fnins.2018.00956。eCollection 2018。

PubMed ID
30686964 (在PubMed
]
文摘

视网膜神经元的功能障碍是致盲的视力损害的主要原因影响全世界儿童和成人的疾病。造成细胞损伤聚胺分解代谢已经证明是一个主要玩家在许多神经退行性条件。我们曾表明,抑制聚胺氧化酶(PAO)使用MDL 72527显著降低视网膜神经细胞退化和细胞死亡信号通路在hyperoxia-mediated视网膜病变。在目前的研究中,我们调查的影响PAO抑制在限制视网膜神经退化模型的全身的NMDA (n -甲基- d)会引起。成年小鼠(8 - 10周大)有intravitreal注射(20 nmol)门冬氨酸或NMLA (N-Methyl-L-aspartate、控制)。腹腔内注射MDL 72527(40毫克/公斤体重/天)或车辆(生理盐水)门冬氨酸或NMLA治疗前24小时,直到动物牺牲(不同的从1到7天)。分析视网膜神经节细胞(RGC)层细胞生存进行视网膜flatmounts。视网膜低温恒温器部分准备疣状,TUNEL检测和视网膜厚度测量。新鲜冷冻视网膜样本用于免疫印迹分析。显著降低神经元生存在RGC层门冬氨酸治疗视网膜NMLA控制,治疗相比,他们所研究的NeuN视网膜flatmounts组织化学染色。 Treatment with MDL 72527 significantly improved survival of NeuN positive cells in the NMDA treated retinas. Excitotoxicity induced neurodegeneration was also demonstrated by reduced levels of synaptophysin and degeneration of inner retinal neurons in NMDA treated retinas compared to controls. TUNEL labeling studies showed increased cell death in the NMDA treated retinas. However, treatment with MDL 72527 markedly reduced these changes. Analysis of signaling pathways during excitotoxic injury revealed the downregulation of pro-survival signaling molecules p-ERK and p-Akt, and the upregulation of a pro-apoptotic molecule BID, which were normalized with PAO inhibition. Our data demonstrate that inhibition of polyamine oxidase blocks NMDA-induced retinal neurodegeneration and promotes cell survival, thus offering a new therapeutic target for retinal neurodegenerative disease conditions.

beplay体育安全吗DrugBank数据引用了这篇文章

药物靶点
药物 目标 生物 药理作用 行动
MDL72527 精胺氧化酶 蛋白质 人类
未知的
抑制剂
细节