{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:23:50Z","timestamp":1791685430651,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T00:00:00Z","timestamp":1691798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science, and Technology, Japan","award":["22K06121"],"award-info":[{"award-number":["22K06121"]}]},{"name":"Ministry of Education, Culture, Sports, Science, and Technology, Japan","award":["23H00394"],"award-info":[{"award-number":["23H00394"]}]},{"name":"Ministry of Education, Culture, Sports, Science, and Technology, Japan","award":["22K19097"],"award-info":[{"award-number":["22K19097"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>A disintegrin and metalloproteinase (ADAM) family proteins are a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell surface protein ectodomains, including amyloid precursor protein (APP). Human ADAM 9, 10, and 17 proteolyze APPs and produce non-amyloid-genic p3 peptides, instead of neurotoxic amyloid-\u03b2 peptides (A\u03b2s; A\u03b240 and A\u03b242), which form fibrils and accumulate in the brain of patients with Alzheimer\u2019s disease (AD). The ADAM family is closely related to snake venom metalloproteinases (SVMPs), which are derived from ancestral ADAMs but act as soluble proteinases. To test the therapeutic potential of SVMPs, we purified SVMPs from Protobothrops flavoviridis venom using metal ion affinity and pooled into a cocktail. Thus, 9 out of 11 SVMPs in the P. flavoviridis genome were identified in the cocktail. SVMPs inhibited A\u03b2 secretion when added to human cell culture medium without affecting APP proteolysis. SVMPs degraded synthetic A\u03b240 and A\u03b242 peptides at the same cleavage site (\u03b1-site of APP) as ADAM9, 10, and 17. SVMPs did not degrade A\u03b2 fibrils but interfered with their formation, assessed using thioflavin-T. Thus, SVMPs have therapeutic potential for AD as an A\u03b2-degrading protease, and the finding adds to the discovery of bioactive peptides from venoms as novel therapeutics.<\/jats:p>","DOI":"10.3390\/toxins15080500","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:40:31Z","timestamp":1692009631000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Metalloproteinase Cocktail from the Venom of Protobothrops flavoviridis Cleaves Amyloid Beta Peptides at the \u03b1-Cleavage Site"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0879-6117","authenticated-orcid":false,"given":"Eugene","family":"Futai","sequence":"first","affiliation":[{"name":"Laboratory of Enzymology, Graduate School of Agricultural Sciences, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology, Graduate School of Agricultural Sciences, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-1658","authenticated-orcid":false,"given":"Shinichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai 980-8578, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-1697","authenticated-orcid":false,"given":"Khadija","family":"Daoudi","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology, Graduate School of Agricultural Sciences, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology, Graduate School of Agricultural Sciences, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisuke","family":"Tomita","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8700-6330","authenticated-orcid":false,"given":"Tomohisa","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology, Graduate School of Agricultural Sciences, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Takeda, S. 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