title: Cu(II) interaction with amyloid-beta peptide: a review of neuroactive mechanisms in AD brains.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the dys-homeostasis of biometal metabolism, the extracellular accumulation of neurotoxic amyloid-beta (Abeta) peptide, the intracellular accumulation of hyperphosphorylated tau and the loss of synapses. Copper plays a key role in AD development. The Abeta peptide and amyloid precursor protein (APP), the parental molecule of Abeta, are modulated by copper in the brain. Increased copper concentration has been found in the AD brain that implies that copper may participate in the pathophysiology of AD. Copper can bind to APP and Abeta, then affects the structure and toxic of APP and Abeta. Some researchers have reported that copper could affect the formation of beta-sheet structure that is widely accepted as toxic secondary structure of Abeta. This review explores the role of copper on the conformation and aggregation of Abeta, and the copper-induced neuroactive mechanisms. Copper may be involved in the following pathways to affect the neuroactivation of Abeta: (1) change of the secondary structure of Abeta; (2) induction of oxidative stress in AD brains, and (3) regulation of cellular signal pathway. Thus, correcting brain copper imbalance may represent a relevant therapeutic target for Alzheimer's disease.
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing, China.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Lin
authors.forename: Han-Chang
authors.initials: HC
authors.lastname: Huang
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Jiang
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D003300:Copper