Prions link cholesterol to neurodegenerationFebruary 12, 2008Prion infection of neurons increases the free cholesterol content in cell membranes. A new study published in the online open access journal BMC Biology suggests that disturbances in membrane cholesterol may be the mechanism by which prions cause neurodegeneration and could point to a role for cholesterol in other neurodegenerative diseases. It is widely believed that prions (protein only infectious material) are the cause of rare progressive neurodegenerative disorders that affect both humans and animals. A prion is an infectious agent made solely of protein. However what is not known is how the prions damage brain cells (neurons). Dr Clive Bate and colleagues from the Royal Veterinary College in the UK compared the amounts of protein and cholesterol in prion-infected neuronal cell lines and primary cortical neurons with uninfected controls. Protein levels were similar but the amount of total cholesterol (a mixture of free and esterified cholesterol) was significantly higher in the infected cell lines. The cholesterol balance was also affected: the amount of free cholesterol increased but that of cholesterol esters reduced, suggesting that prion infection affects cholesterol regulation. The team attempted to reproduce the effects of prions on cholesterol levels, by stimulating cholesterol biosynthesis or by adding exogenous cholesterol. Both approaches resulted in increased amounts of cholesterol esters but not of free cholesterol. The free cholesterol is thought to affect the function of the cell membranes and to lead to abnormal activation of phospholipase A2, an enzyme implicated in the depletion of neurons in prion and Alzheimer's disease. Studies have recently shown that the controlling cholesterol levels within the brain is critical in limiting the development of neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases, multiple sclerosis, and senile dementia. This study now gives far more specific insight into the kind of mechanisms at work. Dr Bate stated: "Our observations raise the possibility that disturbances in membrane cholesterol induced by prions are major triggering events in the neuropathogenesis of prion diseases". BioMed Central |
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| Related Prions Current Events and Prions News Articles The Protein Srebp2 Drives Cholesterol Formation in Prion-Infected Neuronal Cells Which May Promote Prion-Dependent Diseases The regulating protein Srebp2 drives cholesterol formation, which prions need for their propagation, in prion-infected neuronal cells. Cell study explains why younger people more at risk of vCJD Specific cells within the immune system could help explain why younger people are more susceptible to variant CJD, scientists believe. Prion study reveals first direct information about the protein's molecular structure A collaboration between scientists at Vanderbilt University and the University of California, San Francisco has led to the first direct information about the molecular structure of prions. One nano-step closer to weighing a single atom By studying gold nanoparticles with highly uniform sizes and shapes, scientists now understand how they lose energy, a key step towards producing nanoscale detectors for weighing any single atom. Scripps Florida scientists devise accelerated method to determine infectious prion strainsScripps Florida scientists devise accelerated method to determine infectious prion strains Current tests to identify specific strains of infectious prions, which cause a range of transmissible diseases (such as mad cow) in animals and humans, can take anywhere from six months to a year to yield results - a time-lag that may put human populations at risk. Redefining what it means to be a prion Whitehead Institute researchers have quintupled the number of identifiable prion proteins in yeast and have further clarified the role prions play in the inheritance of both beneficial and detrimental traits. Prion discovery gives clue to control of mass gene expression The discovery in common brewer's yeast of a new, infectious, misfolded protein -- or prion -- by University of Illinois at Chicago molecular biologists raises new questions about the roles played by these curious molecules, often associated with degenerative brain diseases like "mad cow" and its human counterpart, Creutzfeldt-Jakob. Antibody key to treating variant CJD, scientists find Scientists at the University of Liverpool have determined the atomic structure of the 'binding' between a brain protein and an antibody that could be key to treating patients with diseases such as variant CJD. Self-regulating molecular 'transformers' control intracellular protein delivery Scientists from the California Institute of Technology (Caltech) have uncovered the Transformer like properties of molecules responsible for carrying and depositing proteins to their correct locations within cells. Study confirms vCJD could be transmitted by blood transfusion The findings underline the importance of precautions against vCJD transmission, such as the Government decision in 2004 to ban blood donations from anyone who had received a blood transfusion since 1980. More Prions Current Events and Prions News Articles |
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