Publications (2)6.18 Total impact
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Article: Aspirin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity in primary midbrain cultures.
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ABSTRACT: Aspirin (ASA) is one of the most widely used nonsteroidal anti-inflammatory drugs. ASA has primarily been used to treat headaches, rheumatic pain, and inflammation, but its therapeutic effects have recently been demonstrated on a range of disorders, including those of the central nervous system. In this study, we investigated whether ASA is neuroprotective in inflammation-mediated neurodegenerative diseases. Pretreatment with ASA reduced the lipopolysaccharide (LPS)-induced degeneration of dopaminergic (DA) neurons in mesencephalic neuron-glia cultures in a dose-dependent manner. The neuroprotective effect of ASA was attributed to the inhibition of microglial activation because of its observed inhibitory effects on LPS-stimulated nitric oxide, tumor necrosis factor-α, and superoxide production by microglial cells. Moreover, ASA increased the production of the anti-inflammatory cytokines transforming growth factor beta-1 and interleukin-10 in neuron-glia cultures after stimulation with LPS. Mechanistic studies revealed that the neuroprotective effects of ASA were mediated through the inhibition of nicotinamide adenine dinucleotide phosphate oxidase (PHOX), a key enzyme for superoxide production in microglia. These results suggest that ASA protects DA neurodegeneration by inhibiting the microglial-mediated oxidative stress/inflammatory response and by regulating the production of anti-inflammatory cytokines.Journal of Molecular Neuroscience 05/2011; 46(1):153-61. · 2.50 Impact Factor -
Article: Insulin like growth factor-1 prevents 1-mentyl-4-phenylphyridinium-induced apoptosis in PC12 cells through activation of glycogen synthase kinase-3beta.
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ABSTRACT: Dopaminergic neurons are lost mainly through apoptosis in Parkinson's disease. Insulin like growth factor-1 (IGF-1) inhibits apoptosis in a wide variety of tissues. Here we have shown that IGF-1 protects PC12 cells from toxic effects of 1-methyl-4-phenylpyridiniumion (MPP(+)). Treatment of PC12 cells with recombinant human IGF-1 significantly decreased apoptosis caused by MPP(+) as measured by acridine orange/ethidium bromide staining. IGF-1 treatment induced sustained phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) as shown by western blot analysis. The anti-apoptotic effect of IGF-1 was abrogated by LY294002, which indirectly inhibits phosphorylation of GSK-3beta. Lithium chloride (LiCl), a known inhibitor of GSK-3beta, also blocked MPP(+)-induced apoptosis. Finally, although IGF-1 enhanced phosphorylation of extracellular signal-regulated kinases ERK1 and 2 (ERK1/2), PD98059, a specific inhibitor of ERK1/2, did not alter the survival effect of IGF-1. Thus, our findings indicate that IGF-1 protects PC12 cells exposed to MPP(+) from apoptosis via the GSK-3beta signaling pathway.Toxicology 04/2010; 271(1-2):5-12. · 3.68 Impact Factor
