{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:13:57Z","timestamp":1778649237377,"version":"3.51.4"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Intervertebral disk degeneration (IDD) is the leading cause of chronic low back pain, yet its link to amino acid metabolic reprogramming remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Three GEO transcriptomes were integrated; amino-acid-metabolism genes were intersected with differentially expressed genes. Core genes were selected by LASSO, SVM and random forest, incorporated into an SHAP-interpretable nomogram, and tested by single-cell analysis,\n                      <jats:italic>in silico<\/jats:italic>\n                      knockout, docking and WB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty-three altered amino acid metabolism-related genes were identified, from which five core genes were screened: CETP, AIFM1, and GM2A were up-regulated; PNPLA2 and AGK were down-regulated. The constructed nomogram prediction model achieved an AUC value of 0.812. Degenerated intervertebral disks exhibited increased immune infiltration; the core genes either suppressed protective matrix genes or impaired stress defense capability. Molecular docking results showed that NVP-AEW541 and EGCG could bind to the AIFM1 protein with a binding free energy of \u221210.7\u202fkcal\/mol; WB confirmed protein trends.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The five-core-gene signature is strongly associated with IDD and may represent a key regulatory pathway, offering a promising diagnostic model and potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1808282","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:46:29Z","timestamp":1778647589000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating multi-omics and machine learning to explore the role of amino acid metabolism in intervertebral disk degeneration"],"prefix":"10.3389","volume":"17","author":[{"given":"Xusheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Spinal Orthopaedics, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]},{"name":"Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital","place":["Sungai Buloh, Selangor, Malaysia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad Nazrun","family":"Shuid","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital","place":["Sungai Buloh, Selangor, Malaysia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Fairudz Mohd","family":"Miswan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital","place":["Sungai Buloh, Selangor, Malaysia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopaedics, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopaedics, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghui","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopaedics, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jungang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopaedics, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopaedics, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Spinal Orthopaedics, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e1231","DOI":"10.1002\/jsp2.1231","article-title":"Intervertebral disc degeneration and how it leads to low back pain","volume":"6","author":"Diwan","year":"2023","journal-title":"JOR 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