Authors
Joud Hirbawi, Adam Zaretsky, Huadong Zhu, Uri Goshtchevsky, Gourab Dey, Emmanuelle Merquiol, Atif Ahmed Siddiqui, Irit Cohen, Galia Blum, Ehud Cohen
Published in
Science advances. Volume 12. Issue 41. Pages eady6048. Oct 09, 2026. Epub Oct 09, 2026.
Abstract
The proteostasis network (PN) safeguards the integrity of proteins by promoting various cellular activities. However, with aging, the PN's competence declines and aggregated proteins accrue within cells. This process underlies the development of neurodegenerative disorders such as Alzheimer's and Huntington's diseases. While the PN functions within cells, proteostasis is regulated across the organism by intertissue communication, which is partially governed by neurons. We previously found that reducing the expression of gtr-1, which encodes a neuronal heterotrimeric guanine nucleotide-binding protein-coupled receptor, mitigates the toxicity of the Alzheimer's disease cause, Aβ peptide. Here, we investigated the mechanism that is acted upon the knockdown of gtr-1 and found that it differentially modulates gene expression profiles, including of neuropeptide-coding genes, and dissimilarly modifies protein aggregation in worms that express distinct proteotoxic proteins. The knockdown of gtr-1 also enhances protein degradation. These findings highlight the roles of neuropeptides as organismal coordinators of proteostasis in the face of distinct proteotoxic challenges.
PMID:
42853952
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.
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