title: Inhibitory effect of human serum albumin on Cu-induced Aβ(40) aggregation and toxicity.
abstract: It has been suggested that the aggregation and cytotoxicity of amyloid-β (Aβ) peptide with transition-metal ions in neuronal cells is involved in the development and progression of Alzheimer's disease (AD). As the most abundant protein in blood plasma and in cerebrospinal fluid, human serum albumin (HSA) can bind Aβ in vivo and subsequently inhibit Aβ fibril growth. However, the roles of albumin in Cu-induced Aβ aggregation and toxicity, and its potential biological relevance to AD therapy, were not stressed enough. Here, we showed that HSA was capable of binding Cu (I) with much higher affinity than Aβ, competitively inhibiting the interaction of Aβ and Cu ions. In the presence of biological reducing agent ascorbate, HSA inhibited Cu (II)/Cu (I)-mediated Aβ40 aggregation, reactive oxygen species production, and neurotoxicity. However, in the absence of Cu (II)/Cu (I), HSA could not effectively inhibit Aβ40 aggregation and neurotoxicity at 24 h (or less) incubation time, but decreased Aβ40 aggregation at much longer incubation (120 h). Our data suggested that through competitively decreasing Cu-Aβ interaction, HSA could effectively inhibit Cu (II)/Cu (I)-induced Aβ40 aggregation and neurotoxicity, and play important roles in regulating redox balance as well as metal homeostasis in AD prevention and therapy.
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, PR China. Electronic address: naihaolu@jxnu.edu.cn.
authors.forename: Naihao
authors.initials: N
authors.lastname: Lu
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, PR China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, PR China. Electronic address: yiyuanpeng@yahoo.com.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Peng
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000188:drug therapy* / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D012709:Serum Albumin; C078592:amyloid beta-protein (1-40); D003300:Copper; D001205:Ascorbic Acid
keywords: Amyloid-β; Aβ aggregation; Cu ions; Human serum albumin; Neurochemistry