{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T08:58:03Z","timestamp":1766048283642},"reference-count":92,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,12,11]],"date-time":"2011-12-11T00:00:00Z","timestamp":1323561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Protein misfolding is a common theme in aging and several age\u2010related diseases such as Alzheimer\u2019s and Parkinson\u2019s disease. The processes involved in the development of these diseases are many and complex. Here, we show that components of the basement membrane (BM), particularly laminin, affect protein integrity of the muscle cells they support. We knocked down gene expression of <jats:italic>epi\u20101,<\/jats:italic> a laminin \u03b1\u2010chain, and found that this resulted in increased proteotoxicity in different <jats:italic>Caenorhabditis elegans<\/jats:italic> transgenic models, expressing aggregating proteins in the body wall muscle. The effect could partially be rescued by decreased insulin\u2010like signaling, known to slow the aging process and the onset of various age\u2010related diseases. Our data points to an underlying molecular mechanism involving proteasomal degradation and HSP\u201016 chaperone activity. Furthermore, <jats:italic>epi\u20101<\/jats:italic>\u2010depleted animals had altered synaptic function and displayed hypersensitivity to both levamisole and aldicarb, an acetylcholine receptor agonist and an acetylcholinesterase inhibitor, respectively. Our results implicate the BM as an extracellular modulator of protein homeostasis in the adjacent muscle cells. This is in agreement with previous research showing that imbalance in neuromuscular signaling disturbs protein homeostasis in the postsynaptic cell. In our study, proteotoxicity may indeed be mediated by the neuromuscular junction which is part of the BM, where laminins are present in high concentration, ensuring the proper microenvironment for neuromuscular signaling. Laminins are evolutionarily conserved, and thus the BM may play a much more causal role in protein misfolding diseases than currently recognized.<\/jats:p>","DOI":"10.1111\/j.1474-9726.2011.00767.x","type":"journal-article","created":{"date-parts":[[2011,11,3]],"date-time":"2011-11-03T18:50:29Z","timestamp":1320346229000},"page":"82-92","source":"Crossref","is-referenced-by-count":11,"title":["A new role for laminins as modulators of protein toxicity in <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1111","volume":"11","author":[{"given":"Louise T.","family":"Jensen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tine H.","family":"M\u00f8ller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon 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