Figure 8. Boosting muscle BDNF rescues impaired axonal transport of signaling endosomes in CMT2D mice.

Top right: Mutant GlyRS aberrantly interacts with the extracellular domain (ECD) of TrkB, the main neurotrophin receptor found at the NMJ. The availability of FL-TrkB in wild-type muscles correlates with the extent of denervation in CMT2D mice, such that higher FL-TrkB levels are associated with reduced NMJ innervation in neuropathy. Middle and top left: CMT2D mice display reduced speed of signaling endosome axonal transport in sciatic, but not median/ulnar, nerves (middle), which is associated with reduced ERK1/2 phosphorylation and decreased endosome adaptor levels in sciatic nerves (middle), as well as dampened CREB activation (top left). Bottom: Injection of mBDNF or AAV8-tMCK-BDNF, but not NT-3, NT-4, or VEGF₁₆₅, into CMT2D muscles completely restores physiological axonal transport in vivo. Figure created using https://www.biorender.com.