{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:22:42Z","timestamp":1768504962728,"version":"3.49.0"},"posted":{"date-parts":[[2023,7,3]]},"group-title":"Neuroscience","reference-count":67,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,7,3]]},"abstract":"<jats:p>Reduction of the production of amyloid beta (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. In this study, we discovered that ceruloplasmin (CP), an important multi-copper oxidase (MCO) in human blood, could degrade A\u03b2 peptides. We also found that the presence of Vitamin C could enhance the degrading effect in a concentration-dependent manner. We then validated the CP-A\u03b2 interaction using total internal reflection fluorescence (TIRF) microscopy, fluorescence photometer, and fluorescence polarization measurement. Based on the above discovery, we hypothesized that other MCOs had similar A\u03b2-degrading functions. Indeed, we found that other MCOs could induce A\u03b2 degradation as well. Remarkably, we revealed that ascorbate oxidase (AO) had the strongest degrading effect among the tested MCOs. Using induced pluripotent stem (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. 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>","DOI":"10.1101\/2023.07.02.547398","type":"posted-content","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T19:25:27Z","timestamp":1688412327000},"source":"Crossref","is-referenced-by-count":0,"title":["Degradation of amyloid beta species by multi-copper oxidases"],"prefix":"10.64898","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Ran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhe","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongzhao","family":"Ran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023070704000750000_2023.07.02.547398v1.1","doi-asserted-by":"crossref","unstructured":"R. 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