The aim of this study was to determine whether there is a relationship between alpha-synuclein (alpha-syn), a key protein in Parkinson’s disease pathogenesis, and abnormalities in glucocerebroside (CC) catabolism that lead to the development of Gaucher disease. We inhibited glucocerebrosidase (GCase) with conduritol B epoxide (CBE) in neuroblastoma cells and mice to test whether a biological link exists between GCase activity and alpha-syn. After CBE exposure, enhanced alpha-syn protein was detected in differentiated cells challenged with CBE as compared to vehicle, with no change in alpha-syn mRNA. In the mouse model, after one injection of CBE, elevated nigral alpha-syn
levels were also detected. Analyses by Western blot and confocal microscopy selleck chemicals revealed that normal alpha-syn distribution was perturbed after CBE exposure with its accumulation apparent within nigral cell bodies as well as astroglia. These findings raise the possibility that alpha-syn may contribute to the cascade
of events that promote neuronal dysfunction in Gaucher disease and are the first to implicate this protein as a plausible biological intersection between Gaucher disease and parkinsonism using a pharmacological model. (C) 2009 Elsevier Inc. All rights E7080 nmr reserved.”
“Little research into neurobehavioural methods and effects occurs in developing countries, where AS1842856 research buy established neurotoxic chemicals continue to pose significant occupational and environmental burdens, and where agents newly identified as neurotoxic are also widespread. Much of the morbidity and mortality associated with neurotoxic agents remains hidden in developing countries as a result of poor case detection, lack of skilled personnel, facilities and equipment for diagnosis, inadequate information systems, limited resources for research and significant competing causes of ill-health,
such as HIV/AIDS and malaria. Placing the problem in a human rights context enables researchers and scientists in developing countries to make a strong case for why the field of neurobehavioural methods and effects matters because there are numerous international human rights commitments that make occupational and environmental health and safety a human rights obligation. (C) 2009 Elsevier Inc. All rights reserved.”
“Exposure to neurotoxic agents represents a concern of high priority in modern society. The nervous system can compensate for the toxic effects caused by low doses, but prolonged and lifetime exposure can also lead to delayed neurodegenerative effects for very low levels. The reported frequency of neurodegenerative diseases is constantly increasing, resulting in serious negative impacts on the health of the worldwide population. Future estimates indicate that Parkinson’s Disease will increase mostly in industrialized countries during the next few years.