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 neurodegenerative disorder, that leads to death in teenage. Another common feature of neurodegenerative diseases is a reduced function of mitochondria, those parts of the cell that produce energy. The connection between altered cholesterol metabolism and neurodegeneration is not yet clear. Cholesterol is an essential part of all mammalian membranes, where it regulates fluidity and protein function. Cholesterol is also the precursor for neurosteroids, steroid hormones made in mitochondria in the brain. Neurosteroids modulate synaptic function, learning and memory and neuronal survival. For both, neurosteroid formation and energy production, cholesterol has to be imported into mitochondria. Using Niemann-Pick Type C disease as an example, we will investigate whether in neurodegeneration cholesterol import into mitochondria is changed, leading to lower neurosteroid levels and impaired energy production. If this is the case, this would be one mechanism by which alterations in cholesterol metabolism cause or worsen neurodegeneration, and could be a new target for therapeutic intervention.