Zhu Kedong, Meng Lanxia, Luo Jiaying, Wen Tingting, Dan Liang, Wang Zhihao, Cao Xuebing, Zhang Zhaohui, Chen Guiqin
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Department of Neurology, Union Hospital, Tongji Medical College, , Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.
J Transl Med. 2024 Dec 30;22(1):1158. doi: 10.1186/s12967-024-06020-x.
Taltirelin, an orally effective thyrotropin-releasing hormone analog, significantly improves motor impairments in rat models of Parkinson's disease (PD) and enhances dopamine release within the striatum. However, the underlying mechanism remains unclear. In this study, a variety of in vivo and in vitro methods, including transcriptomic analysis, were employed to elucidate the effects of Taltirelin on cellular composition and signaling pathways in the striatum of hemi-PD rats. We demonstrated that Taltirelin upregulates the expression of TRHR on striatal GABAergic neurons, which is accompanied by activation of the TRHR-MAPK-RARα-DRD2 pathway. Consequently, Taltirelin induces medium spiny neurons in the striatum to express TH. This discovery provides valuable insights into the potential application of Taltirelin in neurological disorders and offers new directions for drug development.
他替瑞林是一种口服有效的促甲状腺激素释放激素类似物，可显著改善帕金森病（PD）大鼠模型的运动障碍，并增强纹状体内的多巴胺释放。然而，其潜在机制仍不清楚。在本研究中，采用了多种体内和体外方法，包括转录组分析，以阐明他替瑞林对偏侧PD大鼠纹状体中细胞组成和信号通路的影响。我们证明，他替瑞林上调纹状体GABA能神经元上TRHR的表达，并伴随TRHR-MAPK-RARα-DRD2通路的激活。因此，他替瑞林诱导纹状体中的中等棘状神经元表达TH。这一发现为他替瑞林在神经疾病中的潜在应用提供了有价值的见解，并为药物开发提供了新的方向。
