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选择性循环氧化酶-2 抑制剂 NS398 改善了西斯普拉丁诱导的线粒体和认知功能的损伤

Mohammad Abdur Rashid^1,2, Jason J Tang², Ki-Hyun Yoo^1,2

¹Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, United States.

Frontiers in molecular neuroscience

|December 14, 2023

概括

化疗诱导的认知障碍 (CICI) 影响癌症患者. 一项研究发现,用NS398抑制循环氧化酶-2 (COX-2) 可能通过保护线粒体和改善神经元存活来预防CICI.

科学领域:

神经科学是一个神经科学.
在瘤学瘤学.
药理学药理学是指药理学的学科.

背景情况:

化学脑,或化疗诱导的认知障碍 (CICI),显著影响癌症患者的生活质量.
目前,没有有效的治疗方法来治疗或预防CICI,这凸显了对新型治疗策略的需求.

研究的目的:

调查循环氧化酶-2 (COX-2) 和前列腺素E2 (PGE2) 在西斯普拉丁诱导的认知障碍 (CICI) 中的作用.
评估选择性COX-2抑制剂NS398在预防CICI及其相关线粒体功能障碍方面的治疗潜力.

主要方法:

西斯普拉丁用于诱导成年小鼠的CICI和来自诱导多能干细胞 (iPSC) 的人类皮质神经元培养物.
在小鼠海马和人类神经元中测量了COX-2和PGE2的表达.
用NS398评估其对CICI的影响,瘤疗效和线粒体功能 (MMP,ATP产生,细胞活力,树外生长).

主要成果:

西斯普拉丁治疗增加了海马体和神经元培养中的COX-2和PGE2表达.
在未影响西斯的抗瘤作用的情况下,NS398的使用在小鼠中预防了CICI.
NS398治疗前减轻了西斯提诱导的线粒体功能障碍,包括减少MMP,降低ATP生产,降低细胞活力,同时改善神经元外生.

结论:

异常的COX-2炎症途径有助于西斯普拉丁诱导的线粒体损伤和认知障碍.
通过像NS398这样的抑制剂准COX-2信号传递,显示出减轻CICI和改善癌症幸存者的生活质量的治疗策略的希望.

关键词:

NS398 NS398 是一个化学大脑化学大脑西斯普拉丁 (cisplatin) 是一种制剂.认知障碍是一种认知障碍.循环氧基因酶-2 的作用.线粒体中的线粒体.

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