{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:13:57Z","timestamp":1791472437840,"version":"4.3.4"},"reference-count":32,"publisher":"American Society for Clinical Investigation","issue":"9","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["WA2474\/11-1,DFG-SPP1782"],"award-info":[{"award-number":["WA2474\/11-1,DFG-SPP1782"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,7]]},"abstract":"<jats:p>Arrhythmogenic cardiomyopathy (AC) is a genetic disease causing arrhythmia and sudden cardiac death with only symptomatic therapy available at present. Mutations of desmosomal proteins, including desmoglein-2 (Dsg2) and plakoglobin (Pg), are the major cause of AC and have been shown to lead to impaired gap junction function. Recent data indicated the involvement of anti-Dsg2 autoantibodies in AC pathogenesis. We applied a peptide to stabilize Dsg2 binding similar to a translational approach to pemphigus, which is caused by anti-desmoglein autoantibodies. We provide evidence that stabilization of Dsg2 binding by a linking peptide (Dsg2-LP) is efficient to rescue arrhythmia in an AC mouse model immediately upon perfusion. Dsg2-LP, designed to cross-link Dsg2 molecules in proximity to the known binding pocket, stabilized Dsg2-mediated interactions on the surface of living cardiomyocytes as revealed by atomic force microscopy and induced Dsg2 oligomerization. Moreover, Dsg2-LP rescued disrupted cohesion induced by siRNA-mediated Pg or Dsg2 depletion or l-tryptophan, which was applied to impair overall cadherin binding. Dsg2-LP rescued connexin-43 mislocalization and conduction irregularities in response to impaired cardiomyocyte cohesion. These results demonstrate that stabilization of Dsg2 binding by Dsg2-LP can serve as a novel approach to treat arrhythmia in patients with AC.<\/jats:p>","DOI":"10.1172\/jci.insight.130141","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T11:01:37Z","timestamp":1588762897000},"source":"Crossref","is-referenced-by-count":31,"title":["Stabilization of desmoglein-2 binding rescues arrhythmia in arrhythmogenic cardiomyopathy"],"prefix":"10.1172","volume":"5","author":[{"given":"Camilla","family":"Schinner","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Ludwig-Maximilians-Universit\u00e4t (LMU) Munich, Munich, Germany."},{"name":"Department of Biomedicine, University of Basel, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd Markus","family":"Erber","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Ludwig-Maximilians-Universit\u00e4t (LMU) Munich, Munich, 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