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ER-stress signaling and Alzheimer's proteins adjust the quality of human protein synthesis

Cao, Z.; Hartmann, M.; Wagner, M.; Schug, A.; Roesler, R.; Wiese, S.; Yang, Q.; Oswald, F.; Scharffetter-Kochanek, K.; Iben, S.

2026-02-24 cell biology
10.64898/2026.02.23.707382 bioRxiv
Show abstract

Proteostasis is the balance of protein synthesis, protein maintenance and protein degradation. Proteostasis is disturbed in neurodegenerative disorders like Alzheimers disease (AD) of the aging human body. Protein synthesis by the ribosome is the most error-prone process in gene expression. If and how the error-rate of protein synthesis is regulated during human aging and contributes to AD is unknown. Here we show that ribosomal error-rate is adapted in cellular models of human aging, but not in mouse aging. This adaptation involves ER-stress signaling and the Alzheimers disease-related proteins amyloid-beta precursor protein and presenilin 1. Our results suggest that ribosomal error-rate is a relevant parameter in human aging and disease.

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