Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly
- 29 July 2015
- journal article
- research article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 112 (32) , E4465-E4474
Abstract
Significance: Alzheimer’s disease (AD) involves neuron dysfunction and loss. This brain damage is thought to be caused by a small protein, the amyloid β-protein (Aβ), which forms aggregates that are neurotoxic. This neurotoxicity has been explained by multiple mechanisms. We reveal here a new neurotoxic mechanism that involves the interaction between patient-derived Aβ assemblies, termed amylospheroids, and the neuron-specific Na + /K + -ATPase α3 subunit. This interaction causes neurodegeneration through pre-synaptic calcium overload, which explains earlier observations that such neuronal hyperactivation is an early indicator of AD-related neurodegeneration. Importantly, amylospheroid concentrations correlate with disease severity and progression in AD patients. Amylospheroid:neuron-specific Na + /K + -ATPase α3 subunit interactions may be a useful therapeutic target for AD.Keywords
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