Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling in spinal muscular atrophy and amyotrophic lateral sclerosis.

ABSTRACT

Tropomyosin receptor kinase B (TrkB) and its primary ligand brain-derived neurotrophic factor (BDNF) are expressed in the neuromuscular system, where they affect neuronal survival, differentiation, and functions. Changes in BDNF levels and full-length TrkB (TrkB-FL) signaling have been revealed in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), two common forms of motor neuron diseases that are characterized by defective neuromuscular junctions in early disease stages and subsequently progressive muscle weakness. This review summarizes the current understanding of BDNF/TrkB-FL-related research in SMA and ALS, with an emphasis on their alterations in the neuromuscular system and possible BDNF/TrkB-FL-targeting therapeutic strategies. The limitations of current studies and future directions are also discussed, giving the hope of discovering novel and effective treatments.