Product Spotlight: Understanding the Role of Oxysterols in the Brain

Posted on May 12, 2021


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Oxysterols have been proven to be an important part of the brain cholesterol metabolism pathway. Furthermore, changes in the levels of oxysterols in the brain have been shown to contribute to the pathological mechanisms involved in Alzheimer’s Disease (AD). A recent study furthered our knowledge of how oxysterols work in AD pathogenesis by showing that oxysterols present in AD promote astrocyte reactivity which in turn determines the release of several mediators affecting neuronal health and synapses. This increase in astrocyte reactivity is strongly correlated with cognitive decline and neuronal loss. The study proved that oxysterols cause a morphological change in astrocytes and an increase in reactive astrocyte markers and the release of several mediators. While oxysterols are detrimental to neuronal health, they were not overtly neurotoxic. This study, using Avanti’s oxysterol products, paves the way for a better understanding of the role of oxysterols in brain health and for potential novel therapeutic targets for AD.

In continuing our look into oxysterols and brain function, a second study using Avanti's oxysterols examines the sterol transporters belonging to the ABC transporter family in neurons and astrocytes. This family of transporters includes ABCA1, ABCG1, and ABCG4. ABCA1 and ABCG1 regulation is well established, but ABCG4 regulation remains to be fully understood. ABCG4 is thought to transport cholesterol, its synthesis intermediates, and oxysterols, and has recently been found on the blood-brain barrier (BBB). To gain a better understanding of the regulation of ABCG4, a recent study investigated the roles of oxysterols, cholesterol, and cholesterol synthesis intermediates in ABCG4 regulation. The research in this study was conducted using Avanti’s oxysterol, cholesterol, and cholesterol synthesis intermediates. This study showed that ABCG4 expression was induced by a synthetic LXR ligand in astrocytes, but not in neuroblastoma and BBB endothelial cells. They also showed that cholesterol can stabilize ABCG4 as has previously been shown for ABCG1. Further, they were able to show that cholesterol synthesis intermediates, desmosterol, lathosterol, and lanosterol, stabilized ABCG4 transporters more effectively than cholesterol itself. A full understanding of the regulation of the ABCG4 transporter would provide the knowledge necessary to design ways to upregulate its function in brain cells.

These are just a couple of examples of how Avanti's Oxysterols are being studied in human brain health. We invite you to discover the difference that Avanti’s selection of ultra-pure oxysterols can make in your research today!

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To read more about either of these studies, follow the links below.

Oxysterols present in Alzheimer's disease brain induce synaptotoxicity by activating astrocytes: A major role for lipocalin-2

Regulation of ABCG4 transporter expression by sterols and LXR ligands