Roles of Brain-Derived Neurotrophic Factor as an Essential Mediator in Neuronal Functions and Therapeutic Potential of Its Mimetics for Neuroprotection in Neurologic and Psychiatric Disorders

Among neurotrophins, which are composed of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4/5), BDNF has been extensively studied for its physiological role in cell survival and synaptic regulation in the central nervous system (CNS) neurons. BDNF binds to TrkB (a tyrosine kinase) with high affinity and the resulting downstream intracellular signaling cascades play crucial roles in determining cell fate, including neuronal differentiation and maturation of the CNS neurons. It has been well demonstrated that the downregulation/dysregulation of the BDNF/TrkB system is implicated in the pathogenesis of neurologic and psychiatric disorders, such as Alzheimer’s disease (AD) and depression. Interestingly, the effects of BDNF mimetic compounds including flavonoids, small molecules which can activate TrkB-mediated signaling, has been extensively investigated as potential therapeutic strategies for brain diseases, given that p75NTR, a common neurotrophin receptor, also contributes to cell death under a variety of pathological conditions such as neurodegeneration. The present review shows recent advances in the molecular mechanisms underlying the BDNF/TrkB system in neuronal survival and plasticity, providing critical insights into the potential therapeutic impact of BDNF mimetics in pathophysiology of brain diseases.