线粒体皮鲁瓦酸氧化在背部根性细胞中被破坏会导致持续的感觉敏感,并导致普遍的转录基因变化
Md Mamunul Haque1, Panjamurthy Kuppusamy1, Ohannes K Melemedjian1,2,3
1Deptartmen of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States.
Pain
|January 29, 2024
概括
神经生长因子 (NGF) 重新编程感觉神经元代谢,抑制pyruvate氧化和驱动慢性疼痛. 破坏这种新陈代谢途径会导致严重的全体,突出显示了治疗疼痛的新治疗目标.
科学领域:
- 细胞的新陈代谢
- 神经科学是一个神经科学.
- 疼痛研究 疼痛研究
背景情况:
- 代谢对于细胞功能至关重要,调节信号传递和基因表达.
- 变化的新陈代谢有助于癌症和神经退行等疾病.
- 代谢缺陷和神经生长因子 (NGF) 与慢性疼痛有关.
研究的目的:
- 研究NGF如何重新编程感官神经元代谢.
- 为了阐明线粒体酸盐氧化在NGF诱导的疼痛中的作用.
- 探索传感神经元中代谢中断的转录后果.
主要方法:
- 在感官神经元内植入NGF注射.
- 酶抑制测试用于评估代谢途径的参与.
- 纳米孔长读测序用于转录组分析.
- 通过代谢中断诱导全体.
主要成果:
- NGF抑制了线粒体的pyruvate氧化,并增强了乳酸挤出.
- 在NGF上调的乳酸脱酶A和酸盐脱酶激酶1 (PDHK1) 中.
- 扰乱线粒体的pyruvate氧化导致严重的,持久的全氧化症.
- 代谢中断导致了广泛的转录基因变化,包括改变基因表达,拼接和多种尾巴长度.
结论:
- 缺陷的线粒体酸盐氧化作用与慢性疼痛的发展有关.
- NGF重编程感官神经元的新陈代谢,有助于感知敏感化.
- 由代谢体驱动的机制,影响转录基因调节,为难以治疗的疼痛提供了潜在的治疗点.
更多相关视频
相关概念视频
Nociception
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain. Thus, pain helps the...
Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...


