截断的TrkB:在恶性受体中占主导地位的TrkB异型
Jaclyn Merlo1, Fang-Mei Chang2, Michael Tran2
1Center for Pain Therapeutics and Addiction Research, School of Dentistry, University of Texas Health, San Antonio, TX 78229, USA; Department of Endodontics, School of Dentistry, University of Texas Health, San Antonio, TX 78229, USA; Department of Microbiology and Immunology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Integrated Biomedical Sciences (IBMS) Program, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
这项研究揭示了截断的TrkB (TrkBT1) 是三角质受体中的主要形式,调节疼痛信号和神经元存活. 这挑战了关于TrkB受体在疼痛通路中的功能之前的假设.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 疼痛研究 疼痛研究
背景情况:
- TrkB受体信号传递对神经元发育和功能至关重要.
- 截断的TrkB (TrkBT1) 在外围感官神经元,特别是感觉受体中的作用尚不清楚.
- 以前的研究主要将TrkB表达与非感知性感官神经元联系在一起.
研究的目的:
- 研究TrkB异型体在三角感官神经元中的表达和功能作用,特别是感觉受体.
- 挑战TrkBT1的传统观点,认为TrkBT1仅仅是一个主导负面监管机构.
- 阐明TrkBT1对BDNF介导的神经元活动和生存的参与.
主要方法:
- 在三角感官神经元 (nociceptive和non-nociceptive) 中对TrkB异型表达的定量分析.
- 成像用于评估BDNF诱导的恶性受体的反应.
- 使用TrkB抗剂ANA12的药理抑制.
- 在培养的三神经元中进行神经元生存测定.
主要成果:
- TrkBT1是三角体感受体和非感受体中占主导地位的TrkB异型;全长的TrkBTK+仅限于非感受体.
- 通过TrkBT1,BDNF通过TrkBT1在 nociceptors中强化素诱导的流,这种效应被ANA12阻止.
- BDNF促进了感知神经元和非感知神经元的存活,这取决于TrkBT1活动,并被ANA12抑制.
结论:
- TrkBT1作为三角质感受体活动的功能调节器,而不仅仅是一个主导负调节器.
- TrkBT1在BDNF诱导的 nociceptor敏感化和神经元生存中起着双重作用.
- 这些发现为BDNF/TrkB在疼痛中的信号提供了新的见解,并表明了慢性疼痛疾病的潜在治疗点.
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