title: Surfactin exhibits neuroprotective effects by inhibiting amyloid β-mediated microglial activation.
abstract: Microglial-mediated neuroinflammation and neurotoxicity contribute to the pathogenesis of neurodegenerative diseases including Alzheimer's disease; therefore, control of microglial activation and subsequent suppression of neurotoxic pro-inflammatory molecules could provide a potential therapeutic approach for the treatment of such diseases. In this study, we investigated the effects of surfactin, a surfactant from Bacillus subtilis, on oligomeric amyloid β (Aβ)-induced microglial activation and neurotoxicity. Surfactin significantly suppressed expression of MMP-9, iNOS and COX-2, as well as production of ROS, NO, PGE2, TNF-α, IL-1β, IL-6 and MCP-1 in Aβ-stimulated BV-2 microglial cells. Moreover, surfactin markedly inhibited Aβ-induced nuclear translocation and activation of NF-κB as well as phosphorylation of JNK and p38 MAPK. Furthermore, surfactin protected hippocampal HT22 cells from indirect neuronal toxicity mediated by Aβ-treated microglial cells, but had no effect on Aβ-induced direct toxicity to HT22 cells. These results suggest that surfactin impairs the Aβ-induced inflammatory response of microglial cells and confers protection against indirect neurotoxicity to hippocampal cells. Our findings indicate that surfactin may have therapeutic potential for ameliorating Alzheimer's disease as well as other neurodegenerative disorders which involve neuroinflammation.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Keumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: YoungHee
authors.initials: Y
authors.lastname: Kim
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D055666:Lipopeptides / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009410:Nerve Degeneration / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D055666:Lipopeptides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C009365:surfactin peptide; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
keywords: Amyloid β; Inflammation; Microglia; Neurotoxicity; Surfactin