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005     20240112171331.0
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037 _ _ |a DZNE-2023-00908
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Jung, Raimund
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245 _ _ |a A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.
260 _ _ |a Lawrence, KS
|c 2023
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520 _ _ |a During aging, proteostasis capacity declines and distinct proteins become unstable and can accumulate as protein aggregates inside and outside of cells. Both in disease and during aging, proteins selectively aggregate in certain tissues and not others. Yet, tissue-specific regulation of cytoplasmic protein aggregation remains poorly understood. Surprisingly, we found that the inhibition of 3 core protein quality control systems, namely chaperones, the proteasome, and macroautophagy, leads to lower levels of age-dependent protein aggregation in Caenorhabditis elegans pharyngeal muscles, but higher levels in body-wall muscles. We describe a novel safety mechanism that selectively targets newly synthesized proteins to suppress their aggregation and associated proteotoxicity. The safety mechanism relies on macroautophagy-independent lysosomal degradation and involves several previously uncharacterized components of the intracellular pathogen response (IPR). We propose that this protective mechanism engages an anti-aggregation machinery targeting aggregating proteins for lysosomal degradation.
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Caenorhabditis elegans
|2 MeSH
650 _ 2 |a Protein Aggregates
|2 MeSH
650 _ 2 |a Aging
|2 MeSH
650 _ 2 |a Proteasome Endopeptidase Complex
|2 MeSH
650 _ 2 |a Proteostasis
|2 MeSH
650 _ 7 |a Protein Aggregates
|2 NLM Chemicals
650 _ 7 |a Proteasome Endopeptidase Complex
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700 1 _ |a Lechler, Marie
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700 1 _ |a Fernandez-Villegas, Ana
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700 1 _ |a Chung, Chyi Wei
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700 1 _ |a Jones, Harry C
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700 1 _ |a Choi, Yoon Hee
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700 1 _ |a Thompson, Maximilian A
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700 1 _ |a Rödelsperger, Christian
|b 7
700 1 _ |a Röseler, Waltraud
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700 1 _ |a Kaminski Schierle, Gabriele S
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700 1 _ |a Sommer, Ralf J
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700 1 _ |a David, Della
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773 _ _ |a 10.1371/journal.pbio.3002284
|g Vol. 21, no. 9, p. e3002284 -
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856 4 _ |y OpenAccess
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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