Figure 1.

Cholesterol metabolism and homeostasis in the brain. Brain cholesterol is mainly synthesized in the astrocytes and transported into neurons through lipoprotein-ApoEs. Cholesterol is tightly regulated through many factors, such as ApoEs, LDLR, NPC1/2, and CYP46A1. The ApoE4 isoform is highly prevalent in Alzheimer’s disease (AD) pathology, while LRP1 may be a key factor in reducing the risk of AD. The abnormal level of NPC1/2, a factor involved in intracellular cholesterol transporters, is related to AD dementia. In addition, the accumulation of cholesterol in neurons caused by impaired CYP46A1 activity is associated with AD. Beyond its general roles, cholesterol also contributes to post-translational modification and an essential composition of lipid rafts. Disturbed Shh signaling can lead to medulloblastoma brain tumor; meanwhile, dampened lipid rafts may be linked to multiple diseases, such as AD, Parkinson’s disease (PD), and Huntington’s disease (HD). Yellow rectangles indicate upstream factors of brain cholesterol homeostasis. Pink rectangles show the downstream biological role of cholesterol, particularly in neurons. Information obtained from [8,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]. This Figure is created with BioRender.com.