Decreased Phosphorylation Levels of TrkB Neurotrophin Receptor in the Spinal Cords from Patients with Amyotrophic Lateral Sclerosis

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.