Molecular insights into the docking of N-palmitoyl serine (Palmi-Ser) interaction with the nuclear receptor subfamily 4 group A member 2 (NR4A2): Effect of Palmi-Ser on survival rate in the Drosophila model of Parkinson's disease

Abstract

Alternative therapy with medical devices using high-voltage electric potential (HELP) to generate an electric field (EF) is common in Japan. In a previous study, HELP exposure-induced upregulation of N-palmitoyl serine (Palmi-Ser) and N-oleoyl serine (Oleo-Ser) in the plasma of healthy individuals was observed. Recently, we found that Oleo-Ser-stimulated fatty acid-binding protein 1 (FABP1) mRNA expression is sensitive to the peroxisome proliferator-activated receptor-alpha (PPAR-α) antagonist. To discover potential pharmacological targets, an in silico docking simulation of Palmi-Ser or Oleo-Ser with ligand-binding domain (LBD) of NR4A2 was investigated. The binding energies of the LBD of NR4A2 were -8.139 and -8.329 kcal/mol for Palmi-Ser and Oleo-Ser, respectively. Palmi-Ser formed hydrogen bonds with Glu-445, Thr-568, and Thr-595. Alternatively, Oleo-Ser formed hydrogen bonds with Thr-567 and Thr-595. In human neuroblastoma SH-SY5Y cells, Palmi-Ser significantly increased NR4A2 mRNA expression. Under these conditions, Oleo-Ser had no effect on NR4A2 mRNA expression. In the Drosophila model of human α-synuclein-expressed Parkinson's disease, flies treated with Palmi-Ser increased survival rate compared to the vehicle control. Under these conditions, Oleo-Ser had no effect. Palmi-Ser also induced autophagy in human neuroblastoma SH-SY5Y cells. These findings provide new insights into molecular mechanisms of the health benefits for EF therapy through endogenous lipid-derived metabolites.. Nakagawa-Yagi Y (2021) Molecular insights into the docking of N-palmitoyl serine (Palmi-Ser) interaction with the nuclear receptor subfamily 4 group A member 2 (NR4A2): Effect of Palmi-Ser on survival rate in the Drosophila model of Parkinson's disease

Electric-field induced sleep promotion and lifespan extension in Gaucher’s disease model flies: Association with improving ER stress and autophagy

“…If this occurs in vivo , EFs may alleviate GD symptoms by preventing protein aggregation. Our previous study showed that EF treatment elevated N-palmitoyl serine levels in healthy humans, which extended the lifespan of PD model flies (Nakagawa-Yagi et al, 2021). Further studies using Drosophila models of neurodegenerative diseases, such as PD and GD, should be conducted for clarifying the effect of ELF-EFs.…”