24S-Hydroxycholesterol
Chemical compound
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Structure
24S-HC is produced by a hydroxy group substitution at carbon number 24 in cholesterol, catalyzed by the enzyme cholesterol 24-hydroxylase (CYP46A1).
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Function
24S-HC binds to apolipoproteins such as apoE, apoJ, and apoA1 to form HDL-like complexes which can cross the blood–brain barrier more easily than free cholesterol. Thus, 24S-HC production serves as one of several counterbalancing mechanisms for cholesterol synthesis in the brain. After entering general blood circulation and traveling to the liver, 24S-HC can be sulfated, glucuronidated, or converted into bile acids, which can ultimately be excreted.
24S-HC is an agonist of liver X receptors, a class of nuclear receptors that sense oxysterols. In the brain, liver X receptor beta is the primary LXR type, which interacts with 24S-HC. 24S-HC levels sensed by LXRs can regulate the expression of SREBP mRNA and protein, which in turn regulate cholesterol synthesis and fatty acid synthesis.
24S-HC may participate in several aspects of brain development and function, such as axon and dendrite growth or synaptogenesis, as well as acting as a positive allosteric modulator of NMDA receptors. Regulation of 24S-HC metabolism in neurons may play a role in their health and function, as well as their response to injury or disease. Blood plasma levels of 24S-HC may be altered after acute brain injuries such as stroke or in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and multiple sclerosis.