Apolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases

Abstract

Apolipoprotein (apo) E is a multifunctional protein with central roles in lipid metabolism, neurobiology, and neurodegenerative diseases. It has three major isoforms (apoE2, apoE3, and apoE4) with different effects on lipid and neuronal homeostasis. A major function of apoE is to mediate the binding of lipoproteins or lipid complexes in the plasma or interstitial fluids to specific cell-surface receptors. These receptors internalize apoE-containing lipoprotein particles; thus, apoE participates in the distribution/redistribution of lipids among various tissues and cells of the body. In addition, intracellular apoE may modulate various cellular processes physiologically or pathophysiologically, including cytoskeletal assembly and stability, mitochondrial integrity and function, and dendritic morphology and function. Elucidation of the functional domains within this protein and of the three-dimensional structure of the major isoforms of apoE has contributed significantly to our understanding of its physiological and pathophysiological roles at a molecular level. It is likely that apoE, with its multiple cellular origins and multiple structural and biophysical properties, is involved widely in processes of lipid metabolism and neurobiology, possibly encompassing a variety of disorders of neuronal repair, remodeling, and degeneration by interacting with different factors through various pathways.

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

“…As described above, the core members among LDLR family include LDLR,VLDLR, LRP1, LRP1B, LRP4, LRP5, LRP6, megalin, Apoer2 and sorLA/LRP11, which are the confirmed ApoE receptors (16,38,39). In the current study, we found multifarious effects of E2 on LDLR family genes expression during osteoblast differentiation.…”

“…ApoE regulated bone metabolism in mice is possible due to uptake of lipid and lipid soluble vitamins such as vitamin K into osteoblasts (10). It is a common pattern of receptor-mediated endocytosis by the apoE receptors including the LDLR family and HSPGs, for apoE mediated uptake of lipid particles into target cells such as osteoblasts (14)(15)(16). Generally, apoE mediates the interaction of apoE-containing lipoproteins and lipid complexes with the LDLR family.…”

“…ApoE mediates uptake of these particles into target cells such as osteoblasts via receptor-mediated endocytosis by the apoE receptors, which are the lowdensity lipoprotein receptor (LDLR) family and heparan sulfate proteoglycans (HSPGs) (14)(15)(16). ApoE has a strong affinity for and is the main ligand for members of the LDLR family.…”

Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry

“…In addition, the expression of apoE4 in the brain is the major genetic risk factor for early onset Alzheimer's disease (9,10). ApoE4 leads to reduced clearance of extracellular amyloid plaque deposits in the brain (10), increases neuronal degeneration (11), and reduces longevity (12). It is known that apoE can bind to amyloid-β peptide (13), but further mechanistic detail is lacking.…”

Role of Apo E and superoxide dismutase in patients with obstructive lung diseases

“…[10][11][12] It has three major isoforms (Apo E2, Apo E3, and Apo E4) with different effects on lipid and neuronal homeostasis. 13 Intracellular Apo E may regulate various cellular processes physiologically or pathophysiologically. Apo lipoprotein (Apo) E is a multifunctional protein as it intervenes the binding of lipoproteins or lipid complexes in the plasma or interstitial fluids to specific cell-surface receptors as a major function of Apo E. 13 Role of Apo E and superoxide dismutase in patients with obstructive lung diseases Research Ali Mansoor Jasim Al-Ameri et al…”