{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T07:03:29Z","timestamp":1786863809931,"version":"build-2736575974"},"reference-count":24,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,15]]},"abstract":"<jats:p>\n                    Production, aggregation, and clearance of the amyloid \u03b2 peptide (A\u03b2) are important processes governing the initial pathogenesis of Alzheimer\u2019s disease (AD). Inhibition of \u03b2-site amyloid precursor protein (APP) cleaving enzyme (BACE1) (one of two key proteases responsible for A\u03b2 production) as an AD-therapeutic approach so far has failed to yield a successful drug. BACE1 and its homologue BACE2 are frequently inhibited by the same inhibitors. Several genetic and cerebral organoid modeling studies suggest that BACE2 has dose-dependent AD-suppressing activity, which makes its unwanted inhibition potentially counterproductive for AD treatment. The in vivo effects of an unwanted cross inhibition of BACE2 have so far been impossible to monitor because of the lack of an easily accessible pharmacodynamic marker specific for BACE2 cleavage. In this issue of the\n                    <jats:italic>JCI<\/jats:italic>\n                    , work led by Stefan F. Lichtenthaler identifies soluble VEGFR3 (sVEGFR3) as a pharmacodynamic plasma marker for BACE2 activity not shared with BACE1.\n                  <\/jats:p>","DOI":"10.1172\/jci183677","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T14:00:45Z","timestamp":1723644045000},"source":"Crossref","is-referenced-by-count":4,"title":["It\u2019s good to know what to BACE the specificity of your inhibitors on"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4780-3957","authenticated-orcid":true,"given":"Aoife","family":"Murray","sequence":"first","affiliation":[{"name":"The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Mu\u00f1iz-Garc\u00eda","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ali\u0107","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Ni\u017eeti\u0107","sequence":"additional","affiliation":[{"name":"The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,8,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad049"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3983"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00545-1"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5440.735"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00097"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002688200"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505249200"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.09.034"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.10.076"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-46"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00908.x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45896-4"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209859200"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5632com"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300169200"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad9704"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-016-0134-z"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170550"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.04.008"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0806-5"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-00845-5"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16550"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-022-01735-z"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.07.005"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/183677\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:14:09Z","timestamp":1779232449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/183677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,15]]},"references-count":24,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8,15]]},"published-print":{"date-parts":[[2024,8,15]]}},"alternative-id":["10.1172\/JCI183677"],"URL":"https:\/\/doi.org\/10.1172\/jci183677","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,15]]},"article-number":"e183677"}}