Lee Jeongmin, Yon Dong Keon, Choi Yong Sung, Lee Jinseok, Yeo Joon Hyung, Kim Sung Soo, Lee Jae Min, Yeo Seung Geun
Department of Medicine, College of Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea.
Center for Digital Health, Medical Science Research Institute, Kyung Hee University School of Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea.
Curr Issues Mol Biol. 2024 Jul 22;46(7):7769-7781. doi: 10.3390/cimb46070460.
Although several methods are being applied to treat peripheral nerve injury, a perfect treatment that leads to full functional recovery has not yet been developed. SMAD (Suppressor of Mothers Against Decapentaplegic Homolog) plays a crucial role in nerve regeneration by facilitating the survival and growth of nerve cells following peripheral nerve injury. We conducted a systematic literature review on the role of SMAD in this context. Following peripheral nerve injury, there was an increase in the expression of SMAD1, -2, -4, -5, and -8, while SMAD5, -6, and -7 showed no significant changes; SMAD8 expression was decreased. Specifically, SMAD1 and SMAD4 were found to promote nerve regeneration, whereas SMAD2 and SMAD6 inhibited it. SMAD exerts its effects by promoting neuronal survival and growth through BMP/SMAD1, BMP/SMAD4, and BMP/SMAD7 signaling pathways. Furthermore, it activates nerve regeneration programs via the PI3K/GSK3/SMAD1 pathway, facilitating active regeneration of nerve cells and subsequent functional recovery after peripheral nerve damage. By leveraging these mechanisms of SMAD, novel strategies for treating peripheral nerve damage could potentially be developed. We aim to further elucidate the precise mechanisms of nerve regeneration mediated by SMAD and explore the potential for developing targeted nerve treatments based on these findings.
尽管目前有多种方法用于治疗周围神经损伤，但尚未开发出能实现完全功能恢复的完美治疗方法。SMAD（抗五聚体瘫蛋白同源抑制因子）通过促进周围神经损伤后神经细胞的存活和生长，在神经再生中发挥关键作用。我们针对SMAD在这方面的作用进行了系统的文献综述。周围神经损伤后，SMAD1、-2、-4、-5和-8的表达增加，而SMAD5、-6和-7无显著变化；SMAD8表达降低。具体而言，发现SMAD1和SMAD4促进神经再生，而SMAD2和SMAD6抑制神经再生。SMAD通过BMP/SMAD1、BMP/SMAD4和BMP/SMAD7信号通路促进神经元存活和生长来发挥作用。此外，它通过PI3K/GSK3/SMAD1途径激活神经再生程序，促进神经细胞的积极再生以及周围神经损伤后的功能恢复。通过利用SMAD的这些机制，有可能开发出治疗周围神经损伤的新策略。我们旨在进一步阐明SMAD介导神经再生的精确机制，并基于这些发现探索开发靶向神经治疗方法的潜力。
