{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:19:57Z","timestamp":1782299997142,"version":"3.54.5"},"reference-count":67,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,9,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Reduction of the production of amyloid-\u03b2 (A\u03b2) species has been intensively investigated as potential therapeutic approaches for Alzheimer\u2019s disease (AD). However, the degradation of A\u03b2 species, another potential beneficial approach, has been far less explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To investigate the potential of multi-copper oxidases (MCOs) in degrading A\u03b2 peptides and their potential benefits for AD treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We investigated the degradation efficiency of MCOs by using electrophoresis and validated the ceruloplasmin (CP)-A\u03b2 interaction using total internal reflection fluorescence microscopy, fluorescence photometer, and fluorescence polarization measurement. We also investigated the therapeutic effect of ascorbate oxidase (AO) by using induced pluripotent stem (iPS) neuron cells and electrophysiological analysis with brain slices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We discovered that CP, an important MCO in human blood, could degrade A\u03b2 peptides. We also found that other MCOs could induce A\u03b2 degradation as well. Remarkably, we revealed that AO had the strongest degrading effect among the tested MCOs. Using iPS neuron cells, we observed that AO could rescue neuron toxicity which induced by A\u03b2 oligomers. In addition, our electrophysiological analysis with brain slices suggested that AO could prevent an A\u03b2-induced deficit in synaptic transmission in the hippocampus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>To the best of our knowledge, our report is the first to demonstrate that MCOs have a degrading function for peptides\/proteins. Further investigations are warranted to explore the possible benefits of MCOs for future AD treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-240625","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T11:14:40Z","timestamp":1725016480000},"page":"525-539","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Degradation of Amyloid-\u03b2 Species by Multi-Copper Oxidases"],"prefix":"10.1177","volume":"101","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital\/Harvard Medical School, Charlestown, Boston, MA, USA"},{"name":"School of Engineering, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital\/Harvard Medical School, Charlestown, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhe","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of System Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. 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