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Full-Text Articles in Biochemistry
Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen
Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen
Theses & Dissertations
Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …
Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen
Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen
Theses & Dissertations
Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …