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Role of apoE in conformation-prone diseases and atherosclerosis

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Abstract

Three isoforms of human plasma apolipoprotein E (apoE) are ligands to lipoprotein receptors and influence in different manner the synthesis and catabolism of pro-atherogenic triglyceride-rich lipoproteins. Among three isoforms, the apoE4 isoform is associated with increased frequency of atherosclerosis and Alzheimer’s disease (AD). The conformational transitions of β-amyloid (Aβ) influenced by apoE and serum amyloid P (SAP) component are key events in AD development, the accumulation of intermediate diffusible and soluble oligomers of Aβ being of particular significance. SAP and apoE, in a different manner for the three isoforms, serve as “pathological” chaperones during the aggregation of Aβ considered as a conformation-prone process. In turn, apoE consisting of two domains self-associates in solution and intermediate structures differently populated for the three isoforms exist. The different structures of the three isoforms determine their different distribution among various plasma lipoproteins. The structural and metabolic consideration of the common apoE pathway(s) in two pathologies assumes four molecular targets for AD correction: (i) inhibition of the accumulation of diffusible soluble Aβ oligomers; (ii) inhibition of apoE synthesis and secretion by astrocytes, in particular, under lipid-lowering therapy; (iii) inhibition of the binding of apoE and/or SAP to Aβ; (iv) stimulation of the expression of cholesterol transporter ABCA1.

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Abbreviations

AD:

Alzheimer’s disease

apoE:

apolipoprotein E

APP:

amyloid precursor protein

Aβ:

amyloid-β

Ch:

cholesterol

cHSA:

carboxyamidomethylated human serum albumin

HSA:

human serum albumin

LDL:

low density lipoprotein

LDLr:

LDL receptor

LRP:

LDL receptor-related protein

SAP:

serum amyloid P component

SR:

scavenger receptor

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  1. National Research Center for Preventive Medicine, Petroverigsky Pereulok 10, 101990, Moscow, Russia

    A. D. Dergunov

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Published in Russian in Biokhimiya, 2006, Vol. 71, No. 7, pp. 876–881.

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Dergunov, A.D. Role of apoE in conformation-prone diseases and atherosclerosis. Biochemistry (Moscow) 71, 707–712 (2006). https://doi.org/10.1134/S0006297906070029

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