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GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans
Aging causes functional decline and degeneration of neurons and is a major risk factor of neurodegenerative diseases. To investigate the molecular mechanisms underlying neuronal aging, we developed a new pipeline for neuronal proteomic profiling in young and aged animals. While the overall translati...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9770988/ https://www.ncbi.nlm.nih.gov/pubmed/36542715 http://dx.doi.org/10.1126/sciadv.adc9236 |
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author | Wu, Jieyu Wang, Liuyang Ervin, John F. Wang, Shih-Hsiu J. Soderblom, Erik Ko, Dennis Yan, Dong |
author_facet | Wu, Jieyu Wang, Liuyang Ervin, John F. Wang, Shih-Hsiu J. Soderblom, Erik Ko, Dennis Yan, Dong |
author_sort | Wu, Jieyu |
collection | PubMed |
description | Aging causes functional decline and degeneration of neurons and is a major risk factor of neurodegenerative diseases. To investigate the molecular mechanisms underlying neuronal aging, we developed a new pipeline for neuronal proteomic profiling in young and aged animals. While the overall translational machinery is down-regulated, certain proteins increase expressions upon aging. Among these aging–up-regulated proteins, the conserved channel protein TMC-1/Tmc has an anti-aging function in all neurons tested, and the neuroprotective function of TMC-1 occurs by regulating GABA signaling. Moreover, our results show that metabotropic GABA receptors and G protein GOA-1/Goα are required for the anti-neuronal aging functions of TMC-1 and GABA, and the activation of GABA receptors prevents neuronal aging by inhibiting the PLCβ-PKC pathway. Last, we show that the TMC-1–GABA–PKC signaling axis suppresses neuronal functional decline caused by a pathogenic form of human Tau protein. Together, our findings reveal the neuroprotective function of the TMC-1–GABA–PKC signaling axis in aging and disease conditions. |
format | Online Article Text |
id | pubmed-9770988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-97709882022-12-28 GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans Wu, Jieyu Wang, Liuyang Ervin, John F. Wang, Shih-Hsiu J. Soderblom, Erik Ko, Dennis Yan, Dong Sci Adv Biomedicine and Life Sciences Aging causes functional decline and degeneration of neurons and is a major risk factor of neurodegenerative diseases. To investigate the molecular mechanisms underlying neuronal aging, we developed a new pipeline for neuronal proteomic profiling in young and aged animals. While the overall translational machinery is down-regulated, certain proteins increase expressions upon aging. Among these aging–up-regulated proteins, the conserved channel protein TMC-1/Tmc has an anti-aging function in all neurons tested, and the neuroprotective function of TMC-1 occurs by regulating GABA signaling. Moreover, our results show that metabotropic GABA receptors and G protein GOA-1/Goα are required for the anti-neuronal aging functions of TMC-1 and GABA, and the activation of GABA receptors prevents neuronal aging by inhibiting the PLCβ-PKC pathway. Last, we show that the TMC-1–GABA–PKC signaling axis suppresses neuronal functional decline caused by a pathogenic form of human Tau protein. Together, our findings reveal the neuroprotective function of the TMC-1–GABA–PKC signaling axis in aging and disease conditions. American Association for the Advancement of Science 2022-12-21 /pmc/articles/PMC9770988/ /pubmed/36542715 http://dx.doi.org/10.1126/sciadv.adc9236 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Wu, Jieyu Wang, Liuyang Ervin, John F. Wang, Shih-Hsiu J. Soderblom, Erik Ko, Dennis Yan, Dong GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans |
title | GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans |
title_full | GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans |
title_fullStr | GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans |
title_full_unstemmed | GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans |
title_short | GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans |
title_sort | gaba signaling triggered by tmc-1/tmc delays neuronal aging by inhibiting the pkc pathway in c. elegans |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9770988/ https://www.ncbi.nlm.nih.gov/pubmed/36542715 http://dx.doi.org/10.1126/sciadv.adc9236 |
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