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Cholesterol Homeostasis in the Central Nervous System

Posted By Albert Wong
Tags: Neuroscience

The homeostasis and trafficking of cholesterol is an essential component of both the central and peripheral nervous system in maintenance of neuronal tissues. Disturbances in this homeostasis may be due to early onset of neurological diseases such as Alzheimer’s disease, Huntington’s disease, and multiple sclerosis. Apolipoprotein E and Cyp46 (also known as 24S-Cholesterol Hydroxylase) are both important in the homeostasis of cerebral cholesterol6 and thus are of clinical interest in understanding the relationship of these molecules with the pathogenesis of these and potentially other neurodegenerative diseases. Enzo Life Sciences offers the only quantitative 24(S)-hydroxycholesterol ELISA Kit available for neurodegenerative research.

Dopaminergic signaling is associated with reward-motivated behavior and motor control with dysfunction of the dopamine system leading to numerous diseases. For example, degenerative Parkinson’s disease is caused by the loss of dopamine-secreting neurons that leads to motor impairment. Enzo Life Sciences offers a Dopamine ELISA Kit for the quantitative measurement of dopamine concentration in serum, plasma, and cell culture supernatants.



What is Cholesterol? Where is it Produced?



Figure 1: Model of a molecule of cholesterol
Cholesterol is an organic molecule and is an essential structural component of animal cell membranes. Cholesterol supply is crucial for the development and homeostasis of the central nervous system. The liver excretes the non-esterified form into the digestive tract. It is also delivered to other organs as a component of low-density lipoprotein in which cholesterol is included in an esterified form. After binding to the LDL receptor, cholesteryl ester is transported into lysosomes and released in its non-esterified form to be utilized in the construction of cellular manufacture. The cholesterol synthesis pathway comprises more than 20 enzymes and uses acetyl CoA as the starting material. The enzymatic conversion of central nervous system cholesterol to 24-OHC, which readily crosses the blood-brain barrier, is the major pathway for brain cholesterol elimination and brain cholesterol homeostasis maintenance 24-OHC.


Formation of 24-OHC

24-Hydroxycholesterol (24-OHC) is almost exclusively formed in the brain. It is an enzymatically-generated side chain-hydroxylated derivative of cholesterol and is a pivotal marker in the study of cerebral cholesterol homeostasis. However, Cyp46 enzyme converts cholesterol to the more soluble 24-OHC, and this hydroxylated form of cholesterol is able to cross the blood-brain barrier. This conversion allows for the reduction of cholesterol in the brain and the efflux of 24-OHC from the brain into cerebrospinal fluid (CSF) and blood. The flux of 24-OHC has been observed in patients with a variety of neurodegenerative diseases. In patients diagnosed with Alzheimer’s disease, the change in 24S-hydroxycholesterol concentrations may be indicative of different pathogenetic mechanisms and/or the progression of the disease. As in the case of multiple sclerosis, concentrations of 24-OHC have been shown to decrease, likely due to the loss of neuronal cells responsible for the synthesis. The understanding and effects of 24-Hydroxycholesterol could lead to understanding neurodegenerative research that would help scientists come closer to an effective treatment.


Quantitative Tools to Measure 24(S)-Hydroxycholesterol Levels in Samples

Enzo offers a quantitative 24(S)-hydroxycholesterol ELISA Kit available for the measurement of 24(S)- Hydroxycholesterol in tissue culture media, CSF, and tissue homogenate samples. The assay is highly specific to 24-OHC, exhibiting less than 0.02% cross-reactivity to cholesterol, 22-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, and dehydroepiandrosterone (DHEA). The assay returns 24-OHC levels in CSF consistent with levels reported in the literature, and is also suitable for tissue homogenates and tissue culture supernatants, requiring 100 µL or less of sample volume. The assay has a dynamic range from 0.78 to 100 ng/mL and a time to answer of 2 hours, making it a convenient alternative to more labor and instrument-intensive methods such as GC-MS, LC-MS and HPLC-MS.


Quantitative Measurement of Dopamine Levels in Samples



Figure 2: Typical results from our 24(S)-Hydroxycholesterol ELISA Kit (ADI-900-210)



Enzo Life Sciences provides a wide variety of products for your Neuroscience research needs. Our platforms provide a wide range of small molecules, antibodies, and proteins. We offer hundreds of ELISA kits for a wide variety of proteins and hormones with the option of testing multiple sample matrices from a diverse range of species. We are happy to provide simple yet useful tips and guidance for your research needs. Please check out our 10 Tips for Successful ELISA Assays and ELISA Technology Overview, or feel free to contact our Technical Support Service for further assistance.

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