What is it about?
Cerebrosterol is an oxysterol synthesised almost exclusively in the brain. Cerebrosterol originates from hydroxylation of cholesterol, a process important to prevent toxic accumulation of cholesterol on neuron plasma membrane. Enhanced levels of cerebrosterol are toxic in neuron culture, and accumulation of this oxysterol in vivo has been suggested to trigger (or contribute to) neurodegeneration. LCAT is the enzyme esterifying cholesterol for massive transport, as cargo of HDL-like particles, from astrocytes to neurons. These HDL-like particles were shown to cross the blood-brain barrier in mouse, and might represent a system for eliminating excess cholesterol from brain. In this paper LCAT is demonstrated to be able to esterify not only cholesterol but also cerebrosterol. Cerebrosteryl esters, embedded into HDL-like particles, do not penetrate in neurons in culture. Cerebrosterol, when converted by LCAT in ester form, loses its neurotoxicity.
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Why is it important?
The results indicate that LCAT limits neurotoxicity of cerebrosterol, and might highly contribute to eliminate excess cholesterol from brain.
Perspectives
Since LCAT is targeted by oxidative stress, an early event in all types of neurodegeneration, impaired enzyme activity is expected to cause poor shutdown of cerebrosterol neurotoxicity. Moreover, low levels of cerebrosteryl esters in brain-originated circulating HDL reflect impaired LCAT activity in the brain interstitial fluid, a phenomenon that most likely depends on oxidative stress in the brain. Thus measuring the ester fraction in blood cerebrosterol might be a powerful tool to detect oxidative stress in the brain, and early events of neurodegeneration.
Paolo Abrescia
Universita degli Studi di Napoli Federico II
Read the Original
This page is a summary of: The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells, Journal of Neurochemistry, April 2014, Wiley,
DOI: 10.1111/jnc.12713.
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