7,8-Dihydroxyflavone (7,8-DHF), TrkB receptor agonist. Flavonoid.

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

TrkB also known as Neurotrophic Tyrosine Kinase Receptor Type 2 (NTRK2) is a cell surface receptor with a mass of approximately 145 kDa. It binds brain-derived neurotrophic factor (BDNF) and is widely expressed in the central nervous system particularly in areas like the hippocampus cortex and cerebellum. TrkB belongs to the family of receptor tyrosine kinases functioning by catalyzing the transfer of a phosphate group from ATP to specific tyrosine residues on substrate proteins in the receptor triggering downstream signaling cascades.

Biological function summary

TrkB plays essential roles in neuronal survival differentiation and synaptic plasticity. It acts as an important mediator for the effects of neurotrophins primarily BDNF on neurons. While TrkB itself is not part of a multi-protein complex it interacts closely with several adaptor proteins post-activation to propagate survival and proliferation signals within the neuron. These biochemical interactions greatly influence neurodevelopment and cognitive functions.

Pathways

TrkB is a pivotal player in both the MAPK/ERK and PI3K/AKT pathways. Upon BDNF binding TrkB undergoes autophosphorylation triggering these pathways which are critically involved in cell survival and growth. Other proteins such as SHC1 and PLCγ interact with TrkB in these pathways extending the range of cellular responses to neurotrophin signaling facilitating processes like neuronal plasticity and memory formation.

TrkB has significant implications in neurological conditions like Alzheimer's disease and depression. In Alzheimer's disease alterations in TrkB signaling can result in impaired cognitive functions and neuronal loss where it interacts with proteins like amyloid-beta contributing to disease progression. In depression dysfunctional BDNF-TrkB signaling impacts mood regulation and resilience linking TrkB with alterations in serotonin receptor signaling emphasizing its role in mood disorders.