title: β-phenethylamine--a phenylalanine derivative in brain--contributes to oxidative stress by inhibiting mitochondrial complexes and DT-diaphorase: an in silico study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
authors: Muhammed K
authors: MK
authors: Mazumder
authors: Rajib
authors: R
authors: Paul
authors: Anupom
authors: A
authors: Borah
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D003198:Computer Simulation; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010627:Phenethylamines / Q000737:chemistry / Q000494:pharmacology*; D010649:Phenylalanine / Q000737:chemistry / Q000494:pharmacology; D014961:X-Ray Diffraction
chemical_list: D010627:Phenethylamines; C029261:phenethylamine; D010649:Phenylalanine; D016660:NAD(P)H Dehydrogenase (Quinone); D042967:Electron Transport Complex I
keywords: DT-diaphorase; Mitochondrial complex-I; Mitochondrial complex-III; Molecular docking; Neurodegeneration; Oxidative stress; Parkinson's disease
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