{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:19:02Z","timestamp":1791616742594,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["543\/21"],"award-info":[{"award-number":["543\/21"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aberrant protein aggregation jeopardizes cellular functionality and underlies the development of a myriad of late\u2010onset maladies including Alzheimer's disease (AD) and Huntington's disease (HD). Accordingly, molecules that mitigate the toxicity of hazardous protein aggregates are of great interest as potential future therapeutics. Here we asked whether a small peptide, composed of five amino acids (5MER peptide) that was derived from the human pro\u2010inflammatory CD44 protein, could protect model nematodes from the toxicity of aggregative proteins that underlie the development of neurodegenerative disorders in humans. We found that the 5MER peptide mitigates the toxicity that stems from both; the AD\u2010causing A\u03b2 peptide and a stretch of poly\u2010glutamine that is accountable for the development of several disorders including HD, while minimally affecting lifespan. This protection was dependent on the activity of aging\u2010regulating transcription factors and associated with enhanced A\u03b2 and polyQ35\u2010YFP aggregation. A transcriptomic analysis unveiled that the peptide modifies signaling pathways, thereby modulating the expression of various genes, including these, which are known as protein homeostasis (proteostasis) regulators such as <jats:italic>txt\u201013<\/jats:italic> and modifiers of proteasome activity. The knockdown of <jats:italic>txt\u201013<\/jats:italic> protects worms from proteotoxicity to the same extent as the 5MER peptide, suggesting that the peptide activates the transcellular chaperone signaling to promote proteostasis. Together, our results propose that the 5MER peptide should be considered as a component of future therapeutic cocktails for the treatment of neurodegenerative maladies.<\/jats:p>","DOI":"10.1111\/acel.14013","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T05:58:44Z","timestamp":1698472724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A short peptide protects from <scp>age\u2010onset<\/scp> proteotoxicity"],"prefix":"10.1111","volume":"22","author":[{"given":"Hassan","family":"Elsana","sequence":"first","affiliation":[{"name":"The Lautenberg Center of Immunology and Cancer Research The Institute for Medical Research Israel \u2013 Canada (IMRIC), The Hebrew University School of Medicine  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reut","family":"Bruck\u2010Haimson","sequence":"additional","affiliation":[{"name":"Department of 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Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5552-7086","authenticated-orcid":false,"given":"Ehud","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology The Institute for Medical Research Israel \u2013 Canada (IMRIC), The Hebrew University School of Medicine  Jerusalem 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