Cholesterol import into brain mitochondria in niemann-pick type C disease

The brain is the most cholesterol-rich organ in the human body. Alterations in cholesterol metabolism in the brain have been linked to several neurodegenerative disorders, such as Alzheimer¿s disease and Niemann-Pick Type C disease, a fatal inherited disease, that leads to death in teenage. The connection between altered cholesterol metabolism and neurodegeneration is not yet clear. In most neurodegenerative diseases mitochondria also do not function properly. Mitochondria are those parts of the cell that produce energy and make steroids. Steroids in the brain influence communication between nerve cells, learning and memory and nerve cell survival. Cholesterol is an essential part of all cells and of mitochondria. For both functions of mitochondria, energy production and steroid formation, cholesterol has to be imported into mitochondria. Using Niemann-Pick Type C disease as an example, we will investigate how cholesterol is imported into mitochondria in the brain, whether cholesterol import is changed in neurodegenerative disease, and whether this leads to lessened energy production and lower neurosteroid levels. If this is the case, it would be one mechanism by which defects in cholesterol metabolism could cause or worsen neurodegenerative disease, and could be a new target for therapeutic intervention.