Agonistic effect of polyunsaturated fatty acids (PUFAs) and its metabolites on brain-derived neurotrophic factor (BDNF) through molecular docking simulation

Abstract

BackgroundBrain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that is implicated in the regulation of food intake and body weight. Polyunsaturated fatty acids (PUFAs) localised in cell membranes have been shown to alter the levels of BDNF in the brain, suggesting that PUFAs and BDNF could have physical interaction with each other. To decipher the molecular mechanism through which PUFAs modulates BDNF’s activity, molecular docking was performed for BDNF with PUFAs and its metabolites, with 4-Methyl Catechol as a control.ResultsInferring from molecular docking studies, lipoxin A4 (LXA4), and a known anti-inflammatory bioactive metabolite derived from PUFAs, with a binding energy of −3.98 Kcal/mol and dissociation constant of 1.2mM showed highest binding affinity for BDNF in comparison to other PUFAs and metabolites considered in the study. Further, the residues Lys 18, Thr 20, Ala 21, Val 22, Phe 46, Glu 48, Lys 50, Lys 58, Thr 75, Gln 77, Arg 97 and Ile 98 form hot point motif, which on interaction enhances BDNF’s function.ConclusionThese results suggest that PUFAs and their metabolites especially, LXA4, modulate insulin resistance by establishing a physical interaction with BDNF. Similar interaction(s) was noted between BDNF and resolvins and protectins but were of lesser intensity compared to LXA4.

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids

“…These results suggest that PUFAs and their metabolites especially, LXA 4 physically interact with BDNF. Similar interaction(s) was noted between BDNF and resolvins and protectins but were of lesser intensity compared to LXA 4 [111].…”

“…Such a study may pave the way to the development of custom made combinations of various PUFAs with or without BDNF to improve prognosis of patients with autism. Furthermore, significant interaction(s) depicted above between PUFAs/ lipoxins/resolvins/protectins and BDNF [111] also may have relevance in other neurologic/psychiatric conditions such as schizophrenia, Alzheimer's disease, Huntington's disease, and Parkinson's disease [136][137][138].…”

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

“…Indeed, it has been found that ω-3 PUFAs dietary deficiency might increase vulnerability to LPS-induced spatial memory impairment (Delpech et al, 2015). Furthermore, PUFAs may affect basal and stimulated production of serotonin (Kodas et al, 2004), regulate transport of antidepressants through BBB (Kuan et al, 2011) and increase the production of BDNF (Rao et al, 2007;Vetrivel et al, 2012). In turn, the effects of PUFAs on oxidative stress remain the matter of dispute regarding safety issues since pro-oxidative effects have been also reported (Di Nunzio et al, 2016).…”

“…In this study, no significant effects of peripheral levels of Vascular Endothelial Growth Factor (VEGF) and IFN-γ on cognitive functioning were found. Indeed, eotaxin has been found to facilitate cognitive decline during aging by direct inhibition of adult hippocampal neurogenesis (Villeda et al, 2011). Interestingly, eotaxin undergoes a bidirectional transport through BBB that is mediated by binding to the blood cellular components in the slow phase and direct interactions with BBB in the rapid phase (Erickson et al, 2014).…”

A Double-Blind, R CT Testing Beneficial Modulation of B DNF in Middle-Aged, Life Style-Stressed Subjects: A Clue to Brain Protection?

“…Indeed, the hypothesis that PUFAs and their metabolites beneficially interact with BDNF and other neurotrophic factors has been recently suggested [36].…”