In mammals, all cellular membranes contain a specific level of cholesterol influencing their physical and biological properties. Cholesterol is synthesized in every organ and its homeostasis is tightly regulated. In this respect, the central nervous system has an exceptional position: all cholesterol is produced locally. The brain is hence completely independent from nutrition and cholesterol metabolism of the body.

Squalene Synthase catalyzes the first step committed to cholesterol synthesis. Other important cellular pathways such as ATP synthesis and glycosylation are not affected. HMG-CoA reductase is the rate-limiting enzyme of cholesterol biosynthesis.

We investigate the consequences of altered cholesterol/lipid metabolism on the nervous system using a variety of transgenic mouse mutants. Targeting cholesterol biosynthesis by conditional inactivation of Squalene Synthase (link zur SQS-Flox mouse) has proven a powerful tool to study the contribution of individual cell types on the nervous system cholesterol homeostasis. In addition, we address cell biological functions of cholesterol. Analyzing the lipid metabolism in neurodegenerative diseases with the potential development of novel lipid-based therapeutic strategies has become a new focus in my research group.


 

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