Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which is essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, behavior, mental health, learning, memory, stress, pain and apoptosis. BDNF is implicated in various neuronal disorders such as Alzheimer’s disease, Huntington’s disease, depression, and bipolar disorder [1].

BDNF binds to tropomyosin-related kinase B (TrkB), which is a tyrosine kinase receptor [2]. It also binds with low affinity to p75 neurotrophin receptor (p75NTR) [3]. BDNF and its receptors are expressed throughout the central and peripheral nervous system [4],[5].

BDNF signaling is elicited when it dimerizes and binds to TrkB, which results in the receptor dimerization and autophosphorylation [6][7]. The activation of the receptor results in its interaction with molecules such as Shp2 [8], Shc and PLC-gamma [9]. These molecules further interact and modify their downstream targets leading to various neuronal processes. BDNF signaling activates the signaling cascades such as PLC/PKC, PI3K/Akt, Ras/Erk, AMPK/ACC and NFB pathways. BDNF activates PLC/PKC pathway, which leads to release of intracellular calcium [10] and regulation of synaptic plasticity [11]. Activation of PI3K/Akt pathway through BDNF-TrkB interaction inhibits cell apoptosis by decreasing the expression of BIM [12]. However, BDNF-p75NTR interaction leads to apoptosis through JNK pathway [13]. PI3K/Akt also leads to activation of mTOR pathway and subsequently protein synthesis [14]. Ras/Erk signaling is involved in cell proliferation, differentiation and protection of neurons [15]. BDNF signaling leads to nitric oxide production through NFB pathway [16]. It activates Rac and Cdc42 leading to increased neurite outgrowth [17]. It enhances oxidation of fat through AMPK mediated inhibition of ACC [18]. BDNF also regulates the expression of genes leading to processes such as differentiation of dendrites and calcification of cementoblast-like cells [19].

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