The purpose of this study was to investigate the protective effect of creatine against 6-hydroxydopamine (6-OHDA)-induced cell death in neuroblastoma

SH-SY5Y cells and the possible intracellular signaling pathways involved in such effect. Exposure of SH-SY5Y cells to 100-300 mu M of 6-OHDA for 24 h caused a significant concentration-dependent cell death measured as a diminution of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) reduction and as an increase in the extracellular release of lactate dehydrogenase. SH-SY5Y cells incubated for 24 or 48 h with SB203580 creatine (10-5000 mu M) was not cytotoxic. However, pre and co-treatment with creatine (0.3-1000 mu M) for 24 h reduced 6-OHDA-induced toxicity. The protective effect afforded by creatine against 6-OHDA-induced toxicity was reversed by inhibitors of different protein kinases, i.e. phosphatidylinositol-3 kinase (PI3K) (LY294002), Ca2+/calmodulin-dependent protein kinase II (CaMKII) (KN-93), protein kinase A (H-89),

mitogen-activated protein kinase kinase 1/2 (MEK1/2) (PD98059) and protein kinase C (PKC) (chelerythrine). Furthermore, creatine prevented the 6-OHDA-induced dephosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta) at the serine 9 residue. In conclusion, the results of this study show that creatine can protect against 6-OHDA-induced toxicity and its protective mechanism is related to a signaling pathway that involves PI3K, PKC, PKA, CaMKII, MEK1/2 and GSK-3 beta. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Neurologic disease is a major cause of disability in resource-poor countries Omipalisib price and a substantial portion of this disease is due to infections of the CNS. A wide variety of emerging and re-emerging www.selleck.cn/products/BMS-777607.html viruses contribute to

this disease burden. New emerging infections are commonly due to RNA viruses that have expanded their geographic range, spread from animal reservoirs or acquired new neurovirulence properties. Mosquito-borne viruses with expanding ranges include West Nile virus, Japanese encephalitis virus and Chikungunya virus. Zoonotic viruses that have recently crossed into humans to cause neurologic disease include the bat henipaviruses Nipah and Hendra, as well as the primate-derived human immunodeficiency virus. Viruses adapt to new hosts, or to cause more severe disease, by changing their genomes through reassortment (e.g. influenza virus), mutation (essentially all RNA viruses) and recombination (e.g. vaccine strains of poliovirus). Viruses that appear to have recently become more neurovirulent include West Nile virus, enterovirus 71 and possibly Chikungunya virus. In addition to these newer challenges, rabies, polio and measles all remain important causes of neurologic disease despite good vaccines and global efforts toward control. Control of human rabies depends on elimination of rabies in domestic dogs through regular vaccination.