The role of TrkB receptor signaling in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders among the elderly. However, there is no reliable drug for the treatment of AD, which is largely due to the unknown mechanisms and the lack of credible drug targets. Some studies demonstrated the hat the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway may be a potential therapeutic target for AD. As the most widely studied neurotrophin in the brain, BDNF has a high affinity for TrkB receptor and plays an important role in the regulation of neuronal survival, growth, and synaptic plasticity. Mechanistically, TrkB signaling cascade is considered to be the most important way in which BDNF exerts neuroprotective effects. The expression of TrkB receptor was also found to be significantly decreased in AD patients and AD animals compared with the control, suggesting the involvement of TrkB receptor and TrkB-dependent signal in AD pathogenesis. In this review, we aim to discuss the possible role of TrkB-dependent signal in AD pathogenesis, focusing on three major downstream pathways including phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT), extracellular regulated kinase (ERK), and phospholipase C-γ1 (PLC-γ1) pathways.