Английская Википедия:24S-Hydroxycholesterol

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24S-Hydroxycholesterol (24S-HC), also known as cholest-5-ene-3,24-diol or cerebrosterol, is an endogenous oxysterol produced by neurons in the brain to maintain cholesterol homeostasis.[1] It was discovered in 1953 by Alberto Ercoli, S. Di Frisco, and Pietro de Ruggieri, who first isolated the molecule in the horse brain[2] and then demonstrated its presence in the human brain.[3]

Structure

24S-HC is produced by a hydroxy group substitution at carbon number 24 in cholesterol, catalyzed by the enzyme cholesterol 24-hydroxylase (CYP46A1).[4]

Файл:Coversion of cholesterol into 24s-hydroxycholesterol.png
Production of 24S-hydroxycholesterol from cholesterol, as catalyzed by CYP46A1.

Function

24S-HC binds to apolipoproteins such as apoE, apoJ, and apoA1 to form HDL-like complexes[5] 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.[1][6] 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.[7]

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.[5] 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.[8]

24S-HC may participate in several aspects of brain development and function, such as axon and dendrite growth or synaptogenesis,[4] as well as acting as a positive allosteric modulator of NMDA receptors.[9] 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.[10] Blood plasma levels of 24S-HC may be altered after acute brain injuries such as stroke[11] or in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and multiple sclerosis.[12][13]

References

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