title: Regulation of neuronal toxicity of β-amyloid oligomers by surface ATP synthase.
abstract: Alzheimer disease (AD) is characterized by the accumulation of amyloid-β (Aβ) protein and intracellular neurofibrillary tangles. Previous studies have shown that Aβ aggregation is one of the most important initiating factors in the pathogenesis of AD. Oligomers of Aβ cause neurotoxicity, synaptic dysfunction and memory impairments that underlie AD. An increasing number of studies have shown that oligomeric Aβ may bind with a number of surface proteins to mediate its neuronal toxicity. Previously, it was shown that ATP synthase is present on the cell surface and binds with oligomeric Aβ. In the present study, ATP synthase was confirmed to be present on the surface of neurons and oligomeric Aβ was observed to induce neuron damage and expression of amyloid precursor protein (APP) and Fe65 increase. Results showed that inhibition of surface ATP synthase may reduce the neuronal damage by LDH release assay and decrease APP and Fe65 expression by immunofluorescence and western blot analysis. These results confirmed that the cell surface ATP synthase is a binding protein for Aβ on neural cells and suggested that the surface ATP synthase may be involved in the neurotoxic effects of oligomeric Aβ and may be an intervening target of pathogenesis of AD.
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Sanli
authors.initials: S
authors.lastname: Xing
authors.forename: Dingzhu
authors.initials: D
authors.lastname: Shen
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Te
authors.initials: T
authors.lastname: Liu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yu
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D020836:Protein Structure, Quaternary; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; C486242:Apbb1 protein, rat; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D025261:Mitochondrial Proton-Translocating ATPases
keywords: Alzheimer disease; oligomer Aβ, surface ATP synthase; cultured neurons; neuronal toxicity