24S-Hydroxycholesterol

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A cholesterol metabolite involved in brain cholesterol homeostasis



24S-Hydroxycholesterol, also known as cerebrosterol, is a cholesterol metabolite that plays a crucial role in the maintenance of cholesterol homeostasis in the central nervous system. It is primarily produced in the brain and is involved in the regulation of cholesterol levels within the neurons.

Biochemistry[edit | edit source]

24S-Hydroxycholesterol is synthesized from cholesterol by the enzyme cholesterol 24-hydroxylase (CYP46A1), which is predominantly expressed in the brain. This conversion is a critical step in the elimination of excess cholesterol from the brain, as 24S-hydroxycholesterol can cross the blood-brain barrier and enter the systemic circulation.

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Structure of 24S-Hydroxycholesterol

Once in the circulation, 24S-hydroxycholesterol is transported to the liver, where it is further metabolized and excreted in the bile. This process helps to maintain cholesterol balance in the brain, preventing the accumulation of cholesterol that could lead to neurodegenerative diseases.

Physiological Role[edit | edit source]

The primary function of 24S-hydroxycholesterol is to facilitate the removal of cholesterol from the brain. It acts as a signaling molecule that can influence various cellular processes, including the regulation of gene expression and the modulation of neurotransmitter systems.

In addition to its role in cholesterol homeostasis, 24S-hydroxycholesterol has been implicated in the pathophysiology of several neurological disorders. Elevated levels of 24S-hydroxycholesterol have been observed in conditions such as Alzheimer's disease, multiple sclerosis, and Huntington's disease, suggesting a potential role in the progression of these diseases.

Clinical Significance[edit | edit source]

The measurement of 24S-hydroxycholesterol levels in the blood can serve as a biomarker for brain cholesterol metabolism. Alterations in its levels may indicate disruptions in cholesterol homeostasis and could provide insights into the diagnosis and monitoring of neurological disorders.

Research is ongoing to explore the therapeutic potential of modulating 24S-hydroxycholesterol levels in the treatment of neurodegenerative diseases. Understanding the precise mechanisms by which 24S-hydroxycholesterol influences brain function could lead to the development of novel therapeutic strategies.

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Contributors: Prab R. Tumpati, MD