Department of Histology and Embryology, Neurologic Disorders and Regenerative Repair Laboratory, Weifang Medical University, Weifang 261053, China.
Department of Pathology, Weifang Medical University, Weifang 261053, China.
Cells. 2021 Apr 8;10(4):839. doi: 10.3390/cells10040839.
The WNT signaling pathway plays an important role in the physiological and pathophysiological processes of the central nervous system and the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We reviewed the literature pertinent to WNT/β-catenin signaling in ALS from cellular studies, animal models, and human clinical trials. WNT, WNT receptors, and other components of the WNT signaling pathway are expressed in both ALS patients and transgenic mice, and are involved in the pathogenesis of ALS. Studies have shown that abnormal activation of the WNT/β-catenin signaling pathway is related to neuronal degeneration and glial cell proliferation. WNT/Ca signaling is associated with the pro-inflammatory phenotype of microglia; data on the muscle skeletal receptor Tyr kinase receptor in superoxide dismutase-1-G93A mice indicate that gene therapy is necessary for successful treatment of ALS. The varying profiles of lipoprotein receptor-related protein 4 antibodies in different ethnic groups suggest that individual treatment and multifactorial personalized approaches may be necessary for effective ALS therapy. In conclusion, the WNT signaling pathway is important to the ALS disease process, making it a likely therapeutic target.
WNT 信号通路在中枢神经系统的生理和病理生理过程以及神经退行性疾病肌萎缩侧索硬化症（ALS）中发挥着重要作用。我们回顾了与 ALS 中 WNT/β-连环蛋白信号相关的细胞研究、动物模型和人类临床试验的文献。WNT、WNT 受体和 WNT 信号通路的其他成分在 ALS 患者和转基因小鼠中均有表达，并参与 ALS 的发病机制。研究表明，WNT/β-连环蛋白信号通路的异常激活与神经元变性和神经胶质细胞增殖有关。WNT/Ca 信号与小胶质细胞的促炎表型有关；超氧化物歧化酶-1-G93A 小鼠中肌肉骨骼受体酪氨酸激酶受体的数据表明，基因治疗对于成功治疗 ALS 是必要的。不同种族人群脂蛋白受体相关蛋白 4 抗体的不同特征表明，对于有效的 ALS 治疗，可能需要个体化治疗和多因素个性化方法。总之，WNT 信号通路对 ALS 疾病过程很重要，使其成为一个有希望的治疗靶点。
