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Rescuing cholinergic neurons from apoptotic degeneration by targeting of serotonin modulator- and apolipoprotein E-conjugated liposomes to the hippocampus

Authors Kuo YC, Lee YJ

Received 29 September 2016

Accepted for publication 21 November 2016

Published 15 December 2016 Volume 2016:11 Pages 6809—6824

DOI https://doi.org/10.2147/IJN.S123442

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lakshmi Kiran Chelluri

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


Yung-Chih Kuo, Yin-Jung Lee

Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China

Abstract: β-Amyloid (Aβ)-targeting liposomes (LIP) with surface serotonin modulator (SM) and apolipoprotein E (ApoE) were utilized to facilitate the delivery of nerve growth factor (NGF) across the blood–brain barrier (BBB) for neuroprotection in the hippocampus. The therapeutic efficacy of SM- and ApoE-grafted LIP carrying NGF (NGF-SM-ApoE-LIP) was assessed by an in vitro Alzheimer’s disease (AD) model of degenerated SK-N-MC cells and an in vivo AD model of Aβ-insulted Wistar rats. The experimental evidences revealed that the modified SM and ApoE on the surface of LIP increased the permeation of NGF across the BBB without serious damage to structural integrity of tight junction. When compared with free NGF, NGF-SM-ApoE-LIP upregulated the expression of phosphorylated neurotrophic tyrosine kinase receptor type 1 on cholinergic neurons and significantly improved their survival. In addition, NGF-SM-ApoE-LIP could reduce the secretion of acetylcholinesterase and malondialdehyde and rescue hippocampal neurons from apoptosis in rat brains. The synergistic effect of SM and ApoE is promising in the induction of NGF to inhibit the neurotoxicity of Aβ and NGF-SM-ApoE-LIP can be a potent antiapoptotic pharmacotherapy for clinical care of patients with AD.

Keywords:
Alzheimer’s disease, blood–brain barrier, serotonin modulator, apolipoprotein E, nerve growth factor, liposome

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