Does apoE bind to LDL?
Does apoE bind to LDL?
Although LDL particles bind to the LDL receptor through their apolipoprotein B (apo B) and apolipoprotein E (apo E) moieties, other apo E-containing particles, like chylomicron remnants, are not dependent on the LDL receptor for uptake into cells.
How does apoE cause atherosclerosis?
This increases apoA1-rich HDL in plasma, which more effectively removes cellular lipids from circulating monocytes and macrophages, reducing cellular activation and the expression of cell surface adhesion molecules that contribute to vascular recruitment and atherosclerosis.
What is APOE2?
Although the ε2 allele of apolipoprotein E (APOE2) benefits longevity, its mechanism is not understood. The protective effects of the APOE2 on Alzheimer’s disease (AD) risk, particularly through their effects on amyloid or tau accumulation, may confound APOE2 effects on longevity.
Where is LDL receptor located?
the liver
The physiologically important LDL receptors are located primarily in the liver, where their number is regulated by the cholesterol content of the hepatocyte. When the cholesterol content of hepatocytes is raised by ingestion of diets high in saturated fat and cholesterol, LDL receptors fall and plasma LDL levels rise.
How does the cell recognize LDL particles?
Cells express LDL receptor on their plasma membrane. The receptor binds to sites on Apoprotein in LDL. Bound receptors cluster in coated pits and are then endocytosed by clathrin. The endocytic vesicles acidify to become endosomes and the low pH causes a conformational change in the LDL receptor which releases LDL.
Who discovered apolipoprotein E?
It consists of four exons and three introns, with a length of 3597 nucleotides (Das et al., 1985). The polymorphic nature of APOE was first discovered by Utermann (Utermann et al., 1977) and later clarified by Zanis and Breslow (Zannis et al., 1981). Thus, the human gene presents three common alleles: ε2, ε3 and ε4.
How common is APOE2?
ApoE2 is relatively rare, with only 5% incidence, and is considered to be a protective variant against AD. By contrast, as the most potent genetic risk factor for AD, ApoE4 exists in only about 20% of the population; however, it is present in nearly 50% of AD patients.
Why is APOE2 protective?
Viral-mediated APOE*ε2 overexpression Given APOE2 protects against AD likely due to its greater neuroprotective functions than that of APOE3 and APOE4 (Fig. 3), introducing APOE2 into the brain of AD patients who lack APOE*ε2 may have therapeutic effects.
