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Prions Link Cholesterol To Neurodegeneration

Date:
February 12, 2008
Source:
BioMed Central/BMC Biology
Summary:
Prion infection of neurons increases the free cholesterol content in cell membranes. A new study 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.

Prion infection of neurons increases the free cholesterol content in cell membranes. A new study 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.

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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".

Journal reference: Sequestration of free cholesterol in cell membranes by prions correlates with cytoplasmic phospholipase A2 activation. Clive Bate, Mourad Tayebi and Alun Williams. BMC Biology (in press).


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The above story is based on materials provided by BioMed Central/BMC Biology. Note: Materials may be edited for content and length.


Cite This Page:

BioMed Central/BMC Biology. "Prions Link Cholesterol To Neurodegeneration." ScienceDaily. ScienceDaily, 12 February 2008. <www.sciencedaily.com/releases/2008/02/080211195230.htm>.
BioMed Central/BMC Biology. (2008, February 12). Prions Link Cholesterol To Neurodegeneration. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2008/02/080211195230.htm
BioMed Central/BMC Biology. "Prions Link Cholesterol To Neurodegeneration." ScienceDaily. www.sciencedaily.com/releases/2008/02/080211195230.htm (accessed December 21, 2014).

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