Department of Anatomy, School of Medicine (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China.
Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Mol Neurobiol. 2024 Aug;61(8):5194-5205. doi: 10.1007/s12035-023-03887-7. Epub 2024 Jan 3.
Brachial plexus root avulsion (BPRA) injury arises from challenging delivery during childbirth, sports-related incidents, or car accidents, leading to extensive loss of motor neurons (MNs) and subsequent paralysis, including both motor and sensory impairment. Surgical nerve re-implantation cannot effectively restore motor function, and the survival of injured MNs is vital for axon regeneration and re-innervating the target muscles. Therefore, identifying novel molecular targets to improve injured MNs survival is of great significance in the treatment of BPRA injuries. Endothelin-converting enzyme-like 1 (ECEL1), a membrane-bound metallopeptidase, was initially identified as a molecule associated with nerve injuries. Damaged neurons exhibit a significant increase in the expression of ECEL1 following various types of nerve injuries, such as optic nerve injury and sciatic nerve injury. This study aimed to investigate the relationship between ECEL1 overexpression and the survival of injured MNs following BPRA injury. Our results observed a significant elevation in ECEL1 expression in injured MNs and positively correlated with MNs survival following BPRA injury. The transcription of ECEL1 is regulated by the transcription factors c-Jun and ATF3 in the context of BPRA injury, which is consistent with previous other nerve injuries study. In addition, the expression of TrkA gradually decreases in ECEL1-positive MNs and ECEL1 possibly preserves the activity of downstream AKT-GSK3β pathway of TrkA in injured MNs. In conclusion, our results introduce a promising therapeutic molecular target to assist re-implantation surgery for the treatment of BPRA injury.
臂丛神经根撕脱伤 (BPRA) 损伤是由分娩过程中的难产、与运动相关的事故或车祸引起的，导致运动神经元 (MNs) 广泛丧失，随后出现瘫痪，包括运动和感觉功能障碍。手术神经再植入不能有效恢复运动功能，而受伤 MNs 的存活对于轴突再生和重新支配靶肌肉至关重要。因此，确定新的分子靶点以改善受伤 MNs 的存活对于 BPRA 损伤的治疗具有重要意义。内皮素转换酶样 1 (ECEL1) 是一种膜结合金属蛋白酶，最初被鉴定为与神经损伤相关的分子。各种类型的神经损伤，如视神经损伤和坐骨神经损伤后，受损神经元的 ECEL1 表达显著增加。本研究旨在探讨 ECEL1 过表达与 BPRA 损伤后受伤 MNs 存活之间的关系。我们的研究结果观察到 BPRA 损伤后受伤 MNs 中 ECEL1 表达显著升高，并且与 MNs 存活呈正相关。在 BPRA 损伤的情况下，ECEL1 的转录受转录因子 c-Jun 和 ATF3 的调节，这与之前的其他神经损伤研究一致。此外，ECEL1 阳性 MNs 中的 TrkA 表达逐渐降低，ECEL1 可能在受伤 MNs 中保持 TrkA 的下游 AKT-GSK3β 途径的活性。总之，我们的研究结果介绍了一个有前途的治疗分子靶点，以协助 BPRA 损伤的再植入手术治疗。
