Figure 4.
Lipoprotein metabolism and function in the CNS. Lipoprotein particles in the CNS are secreted primarily by astrocytes and, to a lesser extent, by microglia. Lipoproteins exert different functions through binding to LDL receptor family members (1). In particular, binding of lipoproteins to LRP1 in neurons promotes neuronal homeostasis, synaptogenesis, neurite outgrowth, and injury repair (2). Lipoproteins are also ligands for other receptors, such as TREM2, which activates downstream signaling pathways in microglia through the adapter protein DAP12 (3). Microglia play an important role in lipid homeostasis in the brain, including myelin remodeling and repair (4). Age- and disease-status-dependent accumulation of lipid droplets in microglia and in other brain cell types have been reported (5). For different types of lipoprotein particles, see Figure 1. Abbreviations: CNS, central nervous system; HSPG, heparan sulfate proteoglycan; LDLR, low-density lipoprotein receptor; LRP, LDLR-related protein; TREM2; triggering receptor expressed on myeloid cells 2.