c-Jun抑制可以减轻iPSC衍生的感觉神经元中的化疗诱导的神经毒性
Lois Hew1,2, Smilla K Maierhof3,4,5, Andranik Ivanov6
1Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany. lois.hew@charite.de.
Cell death discovery
|November 13, 2025
概括
化疗诱导的周围神经病变 (CIPN) 是一个常见的副作用. 针对感觉神经元中的c-Jun通路显示出预防这种神经毒性的前景.
科学领域:
- 神经科学是一个神经科学.
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 化疗诱导的周围神经病变 (CIPN) 影响了大量的癌症患者.
- 现有的CIPN治疗方法有限,需要新的治疗策略.
研究的目的:
- 使用人类诱导的多能干细胞干细胞衍生的感觉神经元 (iPSC-DSN) 建立一个CIPN体外模型.
- 调查c-Jun路径在CIPN发展中的作用.
- 评估抑制c-Jun的治疗潜力,以预防CIPN.
主要方法:
- 培养人类iPSC-DSN,并将其暴露在各种化疗剂中.
- 评估细胞活力,轴突完整性和电生理功能.
- 进行了转录基因分析,以确定涉及CIPN的分子途径.
- 使用c-Jun N-终端激酶抑制剂 (SP600125) 来阻止c-Jun的活动.
主要成果:
- 化疗剂在iPSC-DSN中诱导神经毒性,其特征是生命力降低,轴突退化和电生理功能障碍.
- 酸化c-Jun的升高与神经元损伤,亡和炎症的基因表达特征相关.
- 使用SP600125抑制c-Jun成功地预防了iPSC-DSN的化疗诱导的神经毒性.
结论:
- 在多种化疗药物中,c-Jun是CIPN病理生理学的关键调解者.
- 抑制c-Jun通路是一个有希望的临床前治疗策略,用于预防CIPN.
相关概念视频
Inhibition of Cdk Activity
5.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
543
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
543


