Apolipoprotein E (ApoE)

Apolipoprotein E (ApoE) is a major cholesterol carrier that plays an important role in maintaining lipid homeostasis in the body.ApoE has a high affinity for lipids and delivers low-density lipoprotein receptor (LDL-R), LDL-R-related protein (LRP), and heparin/heparan sulfate proteoglycans by binding to cholesterol and other essential lipids. In humans, VLDL and IDL containing apoE are removed from the circulation much faster than VLDL and IDL without apoE. In vitro, apoE interacts with phospholipid polar head groups on HDL particles to promote cholesterol ester-rich HDL cores.

 

Structure of ApoE

 

The apolipoprotein E (ApoE) gene is located on the long arm of chromosome 19, and the basic protein consists of 4 exons encoding 299 amino acids.The secondary structure of ApoE consists of 4 structures, the most prominent of which is the α-helix, β-turn.The C-terminus of ApoE is an irregular structure with a large number of amino acid residues. The C-terminus of ApoE is an irregular structure containing a large number of amino acid residues, and through the C-terminal domain, it binds to lipids and participates in the formation of celiac disease, VLDL, IDL, and HDL.ApoE is able to promote the assembly and secretion of VLDL, but overexpression of ApoE leads to the over-production of VLDL and TG, which leads to hypertriacylglycerolemia. Therefore, ApoE regulates the in vivo balance of cholesterol in a relevant way and plays an important role in lipid metabolism.

 

 

Figure 1 Schematic diagram of the molecular structure of ApoE.

 

Biological functions of ApoE

 

 

Human apolipoprotein-E (ApoE) is a polymorphic multifunctional protein that arises from three alleles on a single locus. The human isoforms of ApoE, i.e., ApoE2, ApoE3, and ApoE4, differ by amino acid residues 112 and 158 located outside the N-terminal receptor-binding site, giving rise to proteins with different effects on tissue homeostasis. Thus, ApoE acts through multiple pathways depending on its isoforms, cellular origin, the lipid fraction to which it binds, and multiple genetic and environmental risk factors. In turn, the conceptualization of ApoE's mechanism of action includes: isoform-specific domain-domain interactions; involvement of lipoprotein receptors; influence on cholesterol efflux; maintenance of the blood-brain barrier (BBB); and binding of extracellular molecules, including β-amyloid peptide and heparan sulfate proteoglycans. Among these, ApoE plays an important role in two of the most intractable prototypical human diseases, i.e., Alzheimer's disease (AD) and atherosclerosis.ApoE, a classical complement cascade (CCC) checkpoint inhibitor, affects brain inflammation and atherosclerosis by binding to activated C1q, with the resulting C1q-ApoE complex.

 

Diseases in which ApoE is involved

 

Disease Name

Abbreviation

Hyperlipoproteinemia 3 (HLPP3)

* CMH7

Dilated cardiomyopathy, 2A

* CMD2A

Cardiomyopathy, familial restrictive, 1

* RCM1

 

 

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