title: Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer's disease treatment.
abstract: Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer's disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood-brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD.
authors.affiliation: Department of Chemical Engineering.
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Chemical Engineering.
authors.forename: Che-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Psychology, National Chung Cheng University, Chia-Yi.
authors.forename: Jay-Shake
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Accounting, Providence University, Taichung, Taiwan, Republic of China.
authors.forename: Yung-I
authors.initials: YI
authors.lastname: Lou
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002308:Cardiolipins / Q000494:pharmacology* / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology; D016503:Drug Delivery Systems; D005453:Fluorescence; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010316:Particle Size; D010766:Phosphorylation / Q000187:drug effects; D017208:Rats, Wistar; D055672:Static Electricity; D014909:Wheat Germ Agglutinins / Q000737:chemistry*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002308:Cardiolipins; D008081:Liposomes; D014909:Wheat Germ Agglutinins; D016875:tau Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: Alzheimer’s disease; blood–brain barrier; liposome; neurodegeneration; wheat germ agglutinin; β-amyloid