β-amyloid Peptide Binds and Regulates Ectopic ATP Synthase α-Chain on Neural Surface

ABSTRACT

Accumulation of the amyloid β protein (Aβ) in the brain is an important step in the pathogenesis of Alzheimer's disease. Many molecules could bind with Aβ, among which some molecules mediate Aβ neuronal toxicity. Thus, it is of interest to study the binding proteins of Aβ, and the functions that might be affected by Aβ. In the present study, we observed that accumulation of α-subunit of ATP synthase is associated with aggregates of Aβ proteins in amyloid plaques of amyloid precursor protein/presennillin-1 transgenic mice, and identified the α-subunit of ATP synthase as one of the Aβ 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 Aβ and surface α-subunit of ATP synthase, the extracellular ATP generation was analyzed, which showed that aggregated Aβ partially inhibited the extracellular generation of ATP, but was unable to significantly induce a decrease in cell surface ATP synthase α on neurons. These results suggest that the cell surface ATP synthase α is a binding protein for Aβ on neural cells, the functional inhibition of surface ATP synthase might be involved in machinery of brain malfunction in Aβ-mediated pathogenesis of Alzheimer's disease.

KEYWORDS: :

• aggregated Aβ
• Alzheimer's disease
• ATP production
• ATP synthase α