{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:23:51Z","timestamp":1786976631040,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021ZD0202903"],"award-info":[{"award-number":["2021ZD0202903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373851"],"award-info":[{"award-number":["82373851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Serine Hydroxymethyltransferase 1 (SHMT1) plays a pivotal role in one\u2010carbon metabolism, facilitating the production of SAM. In this study, dysregulation of one\u2010carbon metabolism is reported in both Parkinson's disease (PD) patients and animal models, characterized by significantly downregulated expression of SHMT1. Astrocyte\u2010specific conditional knockout of Shmt1 decreased SAM level, exacerbated motor dysfunction, and dopaminergic neuronal loss in a PD mouse model. While SAM is conventionally generated through the one\u2010carbon cycle, the data indicate that, despite significant alterations in SHMT1, SAM remains unaffected while labeled\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010Serine. Intriguingly, isotopic labeling experiments revealed a significant association between SHMT1 and the production of PDME, an intermediate metabolite of the phosphatidylethanolamine methylation pathway. Consequently, PEMT is discovered as interacting with SHMT1. It is demonstrated that disruption of the interaction between SHMT1 and PEMT leads to SAM depletion, causing H3K4me1 hypomethylation, which in turn reduces the expression of Slc1a2 and Glul. As a result, decoupling of SHMT1 and PEMT in astrocytes ultimately exacerbates neuroexcitotoxicity and dopaminergic neuron loss in PD. Thus, the study elucidates the novel metabolic connection between SHMT1 and PEMT that links the astrocytic one\u2010carbon cycle and membrane phospholipid metabolism in PD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516794","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T08:51:18Z","timestamp":1763628678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Alternative Pathway for Methyl Supply through the Coupling of SHMT1 and PEMT to Maintain Astrocytic Homeostasis in Parkinson's Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Yue\u2010Han","family":"Chen","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211116 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Nanjing Medical University  Nanjing 211116 China"},{"name":"Changzhou Second People's Hospital, Changzhou Medical Center Nanjing Medical University  Changzhou 213000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u2010Hong","family":"Du","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211116 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211116 China"},{"name":"Changzhou Second People's Hospital, Changzhou Medical Center Nanjing Medical University  Changzhou 213000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Nanjing 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