GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in C. elegans.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wu, J; Wang, L; Ervin, JF; Wang, S-HJ; Soderblom, E; Ko, D; Yan, D

Published Date

  • December 21, 2022

Published In

Volume / Issue

  • 8 / 51

Start / End Page

  • eadc9236 -

PubMed ID

  • 36542715

Pubmed Central ID

  • PMC9770988

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.adc9236


  • eng

Conference Location

  • United States