What is it about?

24-Hydroxycholesterol (24OH-C, also called cerebrosterol) is esterified by the enzyme LCAT in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was significantly lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects. Similarly, the level of 24OH-C esters in plasma was significantly lower in patients than in controls. The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls. Oxidative stress reduced LCAT activity in vitro. 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture.

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Why is it important?

The results indicate that reduced levels of 24OH-C esters reflect impaired activity of LCAT in the brain of patients suffering from amyotrophic lateral sclerosis, although astrocytes might be stimulated by accumulation of unesterified 24OH-C to increase their secretion of the ezyme. Moreover, as the value of 24OH-C esters in CSF correlates with that in plasma, the measurement of the level of 24OH-C esters fraction in plasma is an important tool to evaluate the degree of oxidative stress in the brain.

Perspectives

Analysis of the blood level of 24OH-C esters can be used to monitor the progression of amyotrophic lateral sclerosis, and to evaluate the efficacy of current or new treatments for counteracting oxidative stress in this disease as well in other neurodegenerative diseases associated to oxidative damages.

Paolo Abrescia
Universita degli Studi di Napoli Federico II

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This page is a summary of: Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?, Neuroscience Research, April 2016, Elsevier,
DOI: 10.1016/j.neures.2015.09.008.
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