title: Rescuing cholinergic neurons from apoptotic degeneration by targeting of serotonin modulator-and apolipoprotein E-conjugated liposomes to the hippocampus.
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.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China.
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China.
authors.forename: Yin-Jung
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D008081:Liposomes; D009414:Nerve Growth Factors; D012701:Serotonin
keywords: Alzheimer’s disease; apolipoprotein E; blood–brain barrier; liposome; nerve growth factor; serotonin modulator