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模式识别受体在化疗诱导的神经病痛中的作用

Dionéia Araldi¹, Eugen V Khomula¹, Ivan J M Bonet¹

¹Department of Oral and Maxillofacial Surgery, UCSF Pain and Addiction Research Center, University of California at San Francisco, San Francisco, CA 94143, USA.

Brain : a journal of neurology

|October 3, 2023

概括

化疗诱导的周围神经病变 (CIPN) 涉及感官神经元中的TLR4和RAGE等模式识别受体 (PRR). 针对这些PRR显示出预防和逆转CIPN的希望,提供新的治疗途径.

科学领域:

神经科学是一个神经科学.
免疫学免疫学免疫学
药理学药理学是指药理学的学科.

背景情况:

化疗诱导的周围神经病变 (CIPN) 是一种常见的,使人虚弱的副作用,缺乏FDA批准的治疗方法.
CIPN具有临床相似之处,表明涉及感官神经元和模式识别受体 (PRR) 的共同潜在机制.

研究的目的:

为了调查托尔类受体4 (TLR4) 和高级糖化最终产品受体 (RAGE) 在背部根 (DRG) 在CIPN的发展和逆转中的作用.
确定TLR4在CIPN感官神经元的外围和中心终端中的特定贡献.

主要方法:

在CIPN由oxaliplatin,paclitaxel和 bortezomib诱导的老鼠模型中,给予针对TLR4和RAGEmRNA的反感性寡氧核化物 (AS-ODN).
评估TLR4对抗剂在 nociceptors的外围和中央终端的影响.
补丁电生理学,以评估DRG神经元刺激性,以应对化疗暴露.

主要成果:

在所有测试的化疗中,TLR4和RAGE AS-ODN阻止了CIPN的发展.
TLR4 AS-ODN逆转了氧沙利和帕克利塔塞尔诱导的CIPN,但仅暂时减弱了博特佐米布诱导的CIPN.
愤怒AS-ODN逆转了所有三种药物诱导的CIPN.
内,但不是皮内,给予一个TLR4抗剂减弱的CIPN.
奥克沙利普拉丁诱导的DRG神经元刺激性增加是TLR4依赖的.

结论:

PRRs,特别是TLR4和RAGE,在CIPN的发展和进展中发挥着重要作用.
在CIPN中TLR4的作用似乎主要是在中枢神经系统内,影响神经传递.
针对DRG细胞中的PRR提供了一个潜在的治疗策略来管理CIPN.

关键词:

收费类受体4 (TLR4) 是一个收费类受体.博尔特佐米布 (Bortezomib) 是一种药物.化疗诱导的周围神经病变 (CIPN)氧化烯酸是氧化烯酸的一种.帕克利塔克塞尔 (paclitaxel) 是一种药物.对于高级糖化最终产品 (RAGE) 的受体.

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