Molecular signaling of key neurotrophic factors in the brain while the occurrence of affective disorders

Abstract

The COVID-19 pandemic and the increasingly tense political situation worldwide have led to an increase in the incidence of mood disorders. The occurrence of affective disorders is usually associated with neurotransmitters such as serotonin and dopamine; however, modern trends aim at studying the involvement of neurotrophic factors in the mechanisms of mood disorders. This review aimed to summarize and systematize knowledge about key neurotrophic factors and the molecular mechanisms of their relationships. The key metabolic mechanisms of proteins such as brain-derived neurotrophic factor, vascular endothelial growth factor, insulin-like growth factor-1, basic fibroblast growth factor-2, nerve growth factor, and glial cell-line derived neurotrophic factor are considered. Molecular pathways were analyzed, and a complex diagram of a multiple cascade with interconnected reactions was compiled, including each factor. Key molecular targets chosen included nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and cAMP response element-binding protein. The review also presented candidates for the role of limiting factors for these molecular targets. For the NF-kB cascade, neurotrophin receptor p75(NTR) was proposed as a limiting factor, and those for the CREB cascade were intracellular phospholipase C (PLC-γ), binary molecular switches (RAS-GTP), and protein kinase B (AKT).