TrkB Signaling: Beyond the Traditional Model

In the decades since its discovery, our understanding brain-derived-neurotrophic-factor has undergone a transformation. Initially believed to only be expressed during development, BDNF has shown itself to be vital to a wide range of functions in the adult brain, including cell survival and differentiation, synaptic plasticity, and transcription. In turn, BDNF function has been implicated in a number of diseases including depression, cancer, schizophrenia, chronic pain, metabolic disorders, etc. As BDNF became a promising target of therapeutic interventions a more and more detailed assessment of its functioning and an understanding of its high affinity receptor, TrkB, emerged. BDNF-TrkB signaling has become one of the most studied and understood signaling pathways in the mammalian brain. As understanding led to dogma, research aims branched out to external influencers and consequences of this pathway and the functioning of this pathway has been subject to surprisingly little probing with modern, cutting-edge technologies, instead relying on data collected from studies that used the best possible methods at the time, but now are showing their age. Here I will look beyond the conventional model at the implications of new methods and technologies that further reveal layers of intricacy in a signaling system already rife with complexity