Apolipoprotein E3 Containing Nanodiscs as Vehicles for Transport and Targeted Delivery of Flavonoid Luteolin.

Luteolin is a flavonoid that possesses multiple beneficial biological properties, such as anticancer, antioxidant, and anti-inflammatory effects. The objective of this study is to test the hypothesis that luteolin can be transported across a cell via a nanodisc delivery system and delivered to intracellular sites. Luteolin was incorporated into reconstituted high-density lipoprotein complexes made up of apolipoprotein E3 (apoE3) N-terminal domain (apoE3NT) and 1,2-dimystrioyl--3-phosphocholine.

Molecular dynamics simulation of apolipoprotein E3 lipid nanodiscs.

Nanodiscs are binary discoidal complexes of a phospholipid bilayer circumscribed by belt-like helical scaffold proteins. Using coarse-grained and all-atom molecular dynamics simulations, we explore the stability, size, and structure of nanodiscs formed between the N-terminal domain of apolipoprotein E3 (apoE3-NT) and variable number of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) molecules. We study both parallel and antiparallel double-belt configurations, consisting of four proteins per nanodisc.

Isoform-specific modification of apolipoprotein E by 4-hydroxynonenal: protective role of apolipoprotein E3 against oxidative species.

High levels of 4-hydroxynonenal (HNE), arising from lipid peroxidation, and HNE-modified proteins have been identified in postmortem brains of ageing and Alzheimer's disease (AD) patients. The goal of this study is to understand the effect of HNE modification on the structure and function of recombinant apolipoprotein E3 (apoE3) and apolipoprotein E4 (apoE4), which play a critical role in brain cholesterol homeostasis. The two isoforms differ in a single amino acid at position 112: Cys in apoE3 and Arg in apoE4.