| http://purl.uniprot.org/citations/26224839 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26224839 | http://www.w3.org/2000/01/rdf-schema#comment | "Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the molecular identities of pathogenic amyloid β-protein (Aβ) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10-to 15-nm spherical Aβ oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na(+)/K(+)-ATPase α3 subunit (NAKα3). ASPD-binding to NAKα3 impaired NAKα3-specific activity, activated N-type voltage-gated calcium channels, and caused mitochondrial calcium dyshomeostasis, tau abnormalities, and neurodegeneration. NMR and molecular modeling studies suggested that spherical ASPD contain N-terminal-Aβ-derived "thorns" responsible for target binding, which are distinct from low molecular-weight oligomers and dodecamers. The fourth extracellular loop (Ex4) region of NAKα3 encompassing Asn(879) and Trp(880) is essential for ASPD-NAKα3 interaction, because tetrapeptides mimicking this Ex4 region bound to the ASPD surface and blocked ASPD neurotoxicity. Our findings open up new possibilities for knowledge-based design of peptidomimetics that inhibit neurodegeneration in AD by blocking aberrant ASPD-NAKα3 interaction."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1421182112"xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Arai Y."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Ito A."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Kii I."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Inoue M."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Nakamura Y."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Nishiyama T."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Kitamura Y."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Matsui K."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Sato M."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Takahashi H."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Takeda H."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Sawasaki T."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Ohnishi T."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Sakai S."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Teplow D.B."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Takeuchi A."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Muramatsu S."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Nabeshima Y."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Hagiwara M."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Goda N."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Umetsu Y."xsd:string |
| http://purl.uniprot.org/citations/26224839 | http://purl.uniprot.org/core/author | "Tada M."xsd:string |