{"doi":"10.1126/sciadv.adc9236","title":"GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in <i>C. elegans</i>","abstract":"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.","journal":"Science Advances","year":2022,"id":259440,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411014,"name":"Liuyang Wang","orcid":"0000-0001-9556-2361","position":1,"is_corresponding":false},{"id":912098,"name":"John F. Ervin","orcid":"0000-0002-4446-0231","position":2,"is_corresponding":false},{"id":843709,"name":"Shih‐Hsiu J. Wang","orcid":"0000-0002-0358-8159","position":3,"is_corresponding":false},{"id":514967,"name":"Erik J. Soderblom","orcid":"0000-0002-6765-1786","position":4,"is_corresponding":false},{"id":411019,"name":"Dennis C. Ko","orcid":"0000-0002-0113-5981","position":5,"is_corresponding":false},{"id":23421,"name":"Dong Yan","orcid":"0000-0002-7542-1251","position":6,"is_corresponding":false},{"id":912097,"name":"Jieyu Wu","orcid":"0000-0003-3638-9313","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T00:25:58.993402Z","pmid":"36542715","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}