Aim: Till date, the mode of action of β-PEA on neurons is not well illustrated. We tested the hypothesis that β-PEA has the ability to cause oxidative stress by inhibiting the antioxidant enzyme DT-diaphorase and mitochondrial complexes (Complex-I and complex-III).
Methods: Using molecular docking as a tool, we here studied and compared the inhibitory capacity of β-PEA on DT-diaphorase and mitochondrial complexes. Three-dimensional structures of mitochondrial complexes and DT-diaphorase and their ligands were downloaded from the respective data banks, and free energy of binding (docking scores) were determined.
Results: The present finding demonstrated for the first time that β-PEA potentiates reactive oxygen species generation by inhibiting the antioxidant enzyme DT-diaphorase, in addition to the mitochondrial complex-I and complex-III.
Conclusion: As lowering of cellular antioxidant molecules is evident in many neurodegenerative disorders, β-PEA-induced lowering of DT-diaphorase activity may have the capability to cause neurodegeneration, which may be potentiated by its ability to inhibit mitochondrial complexes. Thus, β-PEA-due to its cumulative actions-may be more potent in causing neurodegeneration as compared to other endogenous neurotoxins.
Keywords: DT-diaphorase; Mitochondrial complex-I; Mitochondrial complex-III; Molecular docking; Neurodegeneration; Oxidative stress; Parkinson's disease.
© 2013 John Wiley & Sons Ltd.