Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis

Abstract

VGF-derived neuropeptide TLQP-62 has antidepressant-like properties by increasing hippocampal neurogenesis. This process and VGF levels were found to be impaired in neuropsychiatric disorders. In the present study TLQP-62 was found to promote neurodifferentiation of the human SH-SY5Y cell line by enhancing the expression of several proteins involved in cell cycle regulation, in oxidative stress, in energy metabolism and biosynthesis, and in cytoskeletal organization, promoting neurite outgrowth. All those processes contribute to neurodevelopment and synaptic function. Human TLQP-62 receptor was identified as the G-protein coupled receptor OR5P3, promoting an increase in cAMP levels to initiate signal transduction. TLQP-62 was also found to bind the HSPA8 chaperone. This neuropeptide 3D structure was also found to be mainly disordered but to be transitory with a C-term α-helix that might be stabilized by HSPA8 contributing to its receptor binding and activation. All together these data can contribute to the development of a possible TLQP-62 receptor agonist to be used as a therapy for some neuropsychiatric disorders.