{"doi":"10.1101/2023.10.10.561760","title":"Phosphoglycerate kinase 1 is a central leverage point in Parkinson's disease driven neuronal metabolic deficits","abstract":"Phosphoglycerate kinase 1 (PGK1), the first ATP producing glycolytic enzyme, has emerged as a therapeutic target for Parkinson's Disease (PD), since a potential enhancer of its activity was reported to significantly lower PD risk. We Carried out a suppressor screen of hypometabolic synaptic deficits and demonstrated that PGK1 is the rate limiting enzyme in nerve terminal ATP production. Increasing PGK1 expression in mid-brain dopamine neurons protected against hydroxy-dopamine driven striatal dopamine nerve terminal dysfunction in-vivo and modest changes in PGK1 activity dramatically supressed hypometabolic dysfunction in-vitro. Furthermore, PGK1 is cross-regulated by PARK7(DJ-1), a PD associated molecular chaperone, and synaptic deficits driven by PARK20 (Synaptojanin-1) can be reversed by increasing local synaptic PGK1 activity. These data indicate that nerve terminal bioenergetic deficits may underly a a spectrum of PD susceptibilities and the identification of PGK1 as the limiting enzyme in axonal glycolysis provides a mechanistic underpinning for therapeutic protection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391522,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.961,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1164256,"name":"Aldana M. Antoniazzi","orcid":"0000-0002-0728-3352","position":1,"is_corresponding":false},{"id":1164257,"name":"Santiago R. Unda","orcid":"0000-0001-7319-6794","position":2,"is_corresponding":false},{"id":1164734,"name":"Myung Soo Kokotos","orcid":null,"position":3,"is_corresponding":false},{"id":350311,"name":"Daehun Park","orcid":"0000-0002-2829-1319","position":4,"is_corresponding":false},{"id":317552,"name":"David Eliezer","orcid":"0000-0002-1311-7537","position":5,"is_corresponding":false},{"id":226556,"name":"Michael G. Kaplitt","orcid":"0000-0002-8979-2459","position":6,"is_corresponding":false},{"id":56624,"name":"Pietro De Camilli","orcid":"0000-0001-9045-0723","position":7,"is_corresponding":false},{"id":568496,"name":"Timothy Aidan Ryan","orcid":"0000-0003-2533-9548","position":8,"is_corresponding":false},{"id":1164733,"name":"Alex Kokotos","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:47.408273Z","pmid":"37873141","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":[]}