Sterols in the central nervous system

Purpose of review Aberrations in cerebral cholesterol homeostasis can lead to severe neurological diseases and have been linked to Alzheimer's disease. Many proteins involved in peripheral cholesterol metabolism are also present in the brain. Yet, brain cholesterol metabolism is very different from that in the remainder of the body. This review reports on present insights into the regulation of cerebral cholesterol homeostasis, focusing on cholesterol trafficking between astrocytes and neurons. Recent findings Astrocytes are a major site of cholesterol synthesis. They secrete cholesterol in the form of apolipoprotein E-containing HDL-like particles. After birth, neurons are thought to reduce their cholesterol synthesis and rely predominantly on astrocytes for their cholesterol supply. How exactly neurons regulate their cholesterol supply is largely unknown. A role for the brain-specific cholesterol metabolite, 24(S)-hydroxycholesterol, in this process was recently proposed. Recent findings strengthen the link between brain cholesterol metabolism and factors involved in synaptic plasticity, a process essential for learning and memory functions, as well as regeneration, which are affected in Alzheimer's disease. Summary Insight into the regulation of cerebral cholesterol homeostasis will provide possibilities to modulate the key steps involved and may lead to the development of therapies for the prevention as well as treatment of neurodegenerative diseases such as Alzheimer's disease.

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