{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T01:54:21Z","timestamp":1777686861339,"version":"3.51.4"},"reference-count":59,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JHD"],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:p>Background: Huntington\u2019s disease is an inheritable autosomal dominant disorder caused by an expanded CAG trinucleotide repeat within the Huntingtin gene, leading to a polyglutamine (polyQ) expansion in the mutant protein. Objective: A potential therapeutic approach for delaying or preventing the onset of the disease involves enhancing the degradation of the aggregation-prone polyQ-expanded N-terminal mutant huntingtin (mHTT) exon1 fragment. A few proteases and peptidases have been identified that are able to cleave polyQ fragments with low efficiency. This study aims to identify a potent polyQ-degrading endopeptidase. Methods: Here we used quenched polyQ peptides to identify a polyQ-degrading endopeptidase. Next we investigated its role on HTT turnover, using purified polyQ-expanded HTT fragments and striatal cells expressing mHTT exon1 peptides. Results: We identified insulin-degrading enzyme (IDE) as a novel endopeptidase for degrading polyQ peptides. IDE was, however, ineffective in reducing purified polyQ-expanded HTT fragments. Similarly, in striatal cells expressing mHTT exon1 peptides, IDE did not enhance mHTT turnover. Conclusions: This study shows that despite IDE\u2019s efficiency in degrading polyQ peptides, it does not contribute to the direct degradation of polyQ-expanded mHTT fragments.<\/jats:p>","DOI":"10.3233\/jhd-230583","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T12:17:54Z","timestamp":1713269874000},"page":"201-214","source":"Crossref","is-referenced-by-count":0,"title":["Insulin-Degrading Enzyme Efficiently Degrades polyQ Peptides but not Expanded polyQ Huntingtin Fragments"],"prefix":"10.1177","volume":"13","author":[{"given":"Karlijne W.","family":"Geijtenbeek","sequence":"first","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Medical Biology, Meibergdreef, Amsterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela Santiago","family":"Aranda","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Medical Biology, Meibergdreef, Amsterdam, 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