Underlying molecular mechanisms, that is, paroxetine inhibits iNOS induction and NO generation byLPSJNK1/2 PAR iNOSERK1/2 (baseline activity) PAR PARNOcytokines (TNF- , IL-1 )neurotoxicityFigure 8 Schematic illustration of paroxetine-mediated suppression of neuroinflammation. PAR, paroxetine; LPS, lipopolysaccharide; NO, nitric oxide; iNOS, inducible nitric oxide synthase; , lead to/ activate; , inhibit.Liu et al. Journal of Neuroinflammation 2014, 11:47 http://jneuroinflammation/content/11/1/Page ten ofsuppressing JNK1/2 activation, and attenuates cytokine production by collectively inhibiting JNK1/2 activation and baseline ERK1/2 activity (Figure eight). Since paroxetine is initially set as an antidepressant, our final results give further evidence for the point of view that depression requires neuroinflammatory processes [36,46]. Offered the pathogenic role of inflammation in PD together together with the earlier report displaying paroxetine-mediated prevention of neuronal degeneration in substantia nigra [14], we cautiously recommend that paroxetine may well possibly be useful in alleviating PD progression.Abbreviations DMEM: Dulbecco’s modified Eagle medium; ERK: Extracellular signal-regulated kinase; FBS: Fetal bovine serum; ICR: Imprinting handle region; IL-1: Interleukin 1; iNOS: Inducible nitric oxide synthase; JNK: c-jun N-terminal kinase; LPS: Lipopolysaccharide; MAPK: Mitogen-activated protein kinase; NF-B: Nuclear issue B; NO: nitric oxide; PBS: Phosphate buffered saline; PD: Parkinson’s disease; PCR: Polymerase chain reaction; TNF-: Tumor necrosis element alpha. Competing interests The authors declare no competing interest. Authors’ contributions RPL, MZ, JYW, JJZ, JML, LLZ and SFC performed the experiments; XZ and JHZ made the study; RPL and JHZ wrote the manuscript. All authors read and approved the final manuscript. Acknowledgements This operate was supported by funding from National All-natural Science Foundation of China (31201065 and 31310103026), Zhejiang Provincial Natural Science Foundation (LR13H020002 and LY13H090011), and Overall health Bureau of Zhejiang Province (2013ZDA015, 2013RCA040 and 2013ZB086).213125-87-2 In stock Received: 10 September 2013 Accepted: 24 February 2014 Published: 12 March 2014 References 1. McGeer PL, McGeer EG: Inflammation and neurodegeneration in Parkinson’s illness. Parkinsonism Relat Disord 2004, ten(Suppl 1):S3 7. 2. Block ML, Zecca L, Hong JS: Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007, eight:57?9. 3. Appel SH: Inflammation in Parkinson’s disease: cause or consequence? Mov Disord 2012, 27:1075?077. four. Amor S, Puentes F, Baker D, van der Valk P: Inflammation in neurodegenerative diseases.Formula of 133186-53-5 Immunology 2010, 129:154?69.PMID:34856019 five. Griffiths MR, Gasque P, Neal JW: The several roles from the innate immune method inside the regulation of apoptosis and inflammation inside the brain. J Neuropathol Exp Neurol 2009, 68:217?26. 6. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK: A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 2009, 137:47?9. 7. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH: Mechanisms underlying inflammation in neurodegeneration. Cell 2010, 140:918?34. 8. Hsieh PF, Chia LG, Ni DR, Cheng LJ, Ho YP, Tzeng SF, Chang MH, Hong JS: Behavior, neurochemistry and histology soon after intranigral lipopolysaccharide injection. Neuroreport 2002, 13:277?80. 9. Hunter RL, Cheng B, Choi DY, Liu M, Liu S, Cass WA,.