相关实验视频

Updated: May 15, 2025

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies

Published on: October 6, 2022

神经 p38 MAPK 信号传递有助于西斯普拉丁诱导的外周神经病变

Yugal Goel¹, Donovan A Argueta¹, Kristen Peterson¹

¹Hematology/Oncology, Department of Medicine, University of California, Irvine, CA 92697, USA.

Antioxidants (Basel, Switzerland)

|April 29, 2025

概括

使用neflamapimod抑制p38基因激活蛋白激酶 (MAPK) 激活在背部根结质神经元中,有效降低了化疗诱导的外周神经病变 (CIPN) 和相关疼痛.

科学领域:

神经科学是一个神经科学.
药理学药理学是指药理学的学科.
在瘤学瘤学.

背景情况:

化疗诱导的周围神经病变 (CIPN) 是癌症治疗的常见剂量限制副作用.
在CIPN的发展和进展背后的精确机制仍然不完全理解.
背部根结节 (DRG) 神经元是神经毒性化疗剂的首要目标.

研究的目的:

调查p38基因激活蛋白激酶 (MAPK) 激活在CIPN中DRG神经元中的作用.
评估抑制p38 MAPK激活的治疗潜力,以缓解CIPN.

主要方法:

使用西斯丁治疗的乳腺癌小鼠模型 (C3TAg) 和野生型小鼠 (FVB/N).
在DRG神经元中评估了p38 MAPK酸化和核转位.
服用了neflamapimod,一种特定的p38 MAPKαα (p38α) 抑制剂.
在体外评估了神经元完整性,氧化应激,线粒体功能和亡标记物 (切割的caspase-3).
评估功能性结果,包括机械过敏症,全音症和体内寒冷敏感性.

主要成果:

西斯普拉丁治疗增加了DRG神经元中的p38 MAPK酸化和核转位.
尼夫拉皮莫德在体外和体内抑制了西斯普拉丁诱导的p38 MAPK激活.
尼夫拉皮莫德治疗减少了氧化应激,线粒体功能障碍,并在DRG神经元中切割了caspase-3表达.
在小鼠中,neflamapimod的使用逆转了cisplatin引起的机械和感冒过敏.
尼弗拉米皮莫德治疗可以防止轴突损伤和神经毒性.

结论:

在DRG神经元中的p38 MAPK激活是CIPN的关键调解者.
使用neflamapimod抑制p38 MAPK激活是一种有前途的治疗策略,用于预防和治疗CIPN.
尼夫拉皮莫德可以减轻与CIPN相关的神经毒性和疼痛,但不会影响癌症的进展.

关键词:

在CIPN中,您可以使用CIPN.癌症癌症癌症癌症癌症西斯普拉丁 (cisplatin) 是一种制剂.背部根系团结组织的背部神经元神经元是一个神经元.p38 MAPKK 的时间.疼痛疼痛疼痛疼痛

更多相关视频

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Published on: April 26, 2012

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

相关概念视频

Interactions Between Signaling Pathways

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

MAPK Signaling Cascades

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

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...