Prions associate cholesterol to neurodegeneration

February 12th, 2008 - 4:59 pm ICT by admin  


Washington, Feb 12 (ANI): A new study by researchers at the Royal Veterinary College in the UK has suggested that disturbances in membrane cholesterol may be the mechanism by which prions cause neurodegeneration.

Prions, an infectious agent made solely of protein, are believed to be responsible for rare progressive neurodegenerative disorders that affect both humans and animals.

However what is not known is how the prions damage brain cells (neurons).

For the study, 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.

They found that protein levels were similar but the amount of total cholesterol was significantly higher in the infected cell lines.

They also found that 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 researchers tried 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 believed 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 Alzheimers disease.

Recently studies have shown that the controlling cholesterol levels within the brain is critical in limiting the development of neurodegenerative diseases such as Alzheimers, Parkinsons and prion diseases, multiple sclerosis, and senile dementia.

The new study now gives far more specific insight into the kind of mechanisms at work.

Our observations raise the possibility that disturbances in membrane cholesterol induced by prions are major triggering events in the neuropathogenesis of prion diseases,Dr Bate said.

The study is published in the online open access journal BMC Biology. (ANI)

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