Mutoh T, Sobue G, Hamano T, Kuriyama M, Hirayama M, Yamamoto M, Mitsuma T
The Second Department of Internal Medicine, Fukui Medical University Faculty of Medicine, Japan.
Neurochem Res. 2000 Feb;25(2):239-45. doi: 10.1023/a:1007575504321.
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of specific populations of cranial and spinal motor neurons. In this study, we examined the expression of the high affinity functional receptor for BDNF, TrkB, and assessed the functional state of TrkB by examining the level of phosphorylation on tyrosine residues in ALS spinal cords. The data showed that TrkB-immunoprecipitates prepared from cell-free lysates of ALS spinal cords by use of an anti-TrkB antibody contained much more TrkB protein than from controls. These TrkB proteins expressed in ALS spinal cords, however, are much less phosphorylated on tyrosine residues than those of controls. Moreover, RT-PCR analysis of TrkB mRNA in ALS spinal cords demonstrated that the expression of Trk B mRNA is also upregulated in ALS spinal cords compared with those of controls. These data strongly suggest that there exists an abnormality in TrkB-mediated intracellular signaling in ALS spinal cords and shed a light on the possibility of the therapeutic intervention by normalizing this intracellular signaling.
肌萎缩侧索硬化症（ALS）的特征是特定的颅神经和脊髓运动神经元群体发生选择性退化。在本研究中，我们检测了脑源性神经营养因子（BDNF）的高亲和力功能性受体TrkB的表达，并通过检测ALS脊髓中酪氨酸残基的磷酸化水平来评估TrkB的功能状态。数据显示，使用抗TrkB抗体从ALS脊髓的无细胞裂解物中制备的TrkB免疫沉淀物所含的TrkB蛋白比对照组多得多。然而，这些在ALS脊髓中表达的TrkB蛋白在酪氨酸残基上的磷酸化程度比对照组低得多。此外，对ALS脊髓中TrkB mRNA的逆转录聚合酶链反应（RT-PCR）分析表明，与对照组相比，ALS脊髓中TrkB mRNA的表达也上调。这些数据强烈表明，ALS脊髓中TrkB介导的细胞内信号传导存在异常，并为通过使这种细胞内信号传导正常化进行治疗干预的可能性提供了线索。
