Beta-Amyloid Peptide Binds And Regulates Ectopic Atp Synthase Alpha-Chain On Neural Surface
INTERNATIONAL JOURNAL OF NEUROSCIENCE(2012)
摘要
Accumulation of the amyloid beta protein (A beta) in the brain is an important step in the pathogenesis of Alzheimer's disease. Many molecules could bind with A beta, among which some molecules mediate A beta neuronal toxicity. Thus, it is of interest to study the binding proteins of A beta, and the functions that might be affected by A beta. In the present study, we observed that accumulation of alpha-subunit of ATP synthase is associated with aggregates of A beta proteins in amyloid plaques of amyloid precursor protein/presennillin-1 transgenic mice, and identified the alpha-subunit of ATP synthase as one of the A beta binding proteins on the plasma membrane of neural cells by Western blot and mass spectrometry. In order to evaluate the consequences of the interaction between A beta and surface alpha-subunit of ATP synthase, the extracellular ATP generation was analyzed, which showed that aggregated A beta partially inhibited the extracellular generation of ATP, but was unable to significantly induce a decrease in cell surface ATP synthase alpha on neurons. These results suggest that the cell surface ATP synthase alpha is a binding protein for A beta on neural cells, the functional inhibition of surface ATP synthase might be involved in machinery of brain malfunction in A beta-mediated pathogenesis of Alzheimer's disease.
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关键词
aggregated A beta, Alzheimer's disease, ATP production, ATP synthase alpha
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