Deletion of the BDNF receptor TrkB.T1 alleviated muscle weakness and motoneuron cell death of spinal cord in the G93A SOD1 animal model of ALS, indicating TrkB.T1 may limit the neuroprotective BDNF signaling to motoneurons via a non-cell autonomous mechanism, which providing new understanding of the reasons for past clinical failures (Yanpallewar et al., 2021). This evidence concerns the gene BDNF and amyotrophic lateral sclerosis.