Rational Protein Molecular Design of Hydrophobic Interior-Modified Ferritin Enables Efficient Lycopene Delivery for Ameliorating Aging-Related Cognitive Impairment.

Hemeng Ma, Geng Cao, Xiaoyu Xia, Shuhong Ye, Jiachen Zang, Shuzhen Cheng, Ming Du

State Key Laboratory of Marine Food Processing & Safety Control, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.State Key Laboratory of Marine Food Processing & Safety Control, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China. · pubmed

Paper

Abstract

Lycopene shows potential against aging-related cognitive decline but suffers from poor stability, low blood-brain barrier penetration, and inefficient delivery. Native rHuHF is biocompatible yet achieves only ∼6% lycopene encapsulation due to its hydrophilic cavity. Here, a recombinant mutant human heavy-chain ferritin (rXHF) with a hydrophobic interior was engineered by replacing four polar residues with tryptophan. rXHF maintains the 24-mer nanocage structure and exhibits enhanced hydrophobicity. It achieves 74.9 ± 2.5% encapsulation efficiency and 17.8 ± 0.6% loading efficiency (2.9-fold that of rHuHF). At a molar ratio of 1:200, the DPPH scavenging rate reached 30.06 ± 9.2%. In D-galactose-induced aging mice, rXHF-LYC dose-dependently improved spatial learning/memory, reduced hippocampal senescence, and modulated oxidative stress, neuroinflammation, and synaptic plasticity via BDNF/TrkB. PC12 assays confirmed endocytic uptake, ROS scavenging, apoptosis inhibition, and preserved acetylcholine synthesis. Thus, hydrophobic ferritin modification enables brain-targeted lycopene delivery, offering a novel strategy for age-related neurodegenerative diseases.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that engineered hydrophobic ferritin can enhance lycopene delivery to ameliorate aging-related cognitive impairment. The research addresses a specific aspect of aging-related cognitive decline, focusing on improving delivery mechanisms for a compound that may have protective effects against neurodegeneration, thus contributing to the understanding of interventions in age-related diseases.

Author of this paper? Send a correction.