Recombinant neurotrophin-3 with the ability to penetrate the blood-brain barrier: A new strategy against Alzheimer's disease.

Autor: Ding X; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China., Zuo Y; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China., Liu Z; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China., Sun Y; Department of Endocrinology, Jilin University Second Hospital, Changchun, Jilin 130022, PR China., Wang L; State key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Changchun, Jilin 130022, PR China., Xie Y; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China., Liu G; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China., Liu C; College of Pharmacy, Beihua University, Jilin, Jilin 132013, PR China. Electronic address: liuchangbhu@163.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Dec 30, pp. 139359. Date of Electronic Publication: 2024 Dec 30.
DOI: 10.1016/j.ijbiomac.2024.139359
Abstrakt: This study aims to develop and evaluate a novel therapeutic strategy for Alzheimer's disease (AD) by overcoming the blood-brain barrier (BBB) limitations of Neurotrophin-3 (NT-3). NT-3, a critical neurotrophic factor, plays essential roles in hippocampal neuron growth, survival, and synaptic plasticity, making it a promising candidate for AD treatment. However, its clinical application is hindered by its inability to cross the BBB. To address this, we utilized genetic engineering techniques to fuse the TAT transmembrane peptide with NT-3, producing a recombinant NT-3 (T-NT-3) with enhanced membrane-penetrating capability. Protein characterization confirmed that T-NT-3 possesses good stability and the ability to cross the BBB. In vitro experiments demonstrated that T-NT-3 inhibits oxidative stress, apoptosis, and inflammatory responses in neural cells by activating TrkC receptors and suppressing M1 microglial activation. In vivo, T-NT-3 improved cognitive and memory impairments in APP/PS1 mice and reduced AD-associated pathological changes. These findings highlight the mechanisms by which T-NT-3 alleviates hippocampal neurotoxicity, providing a foundation for its future application as a recombinant protein therapy for AD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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