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Neurosci."],"abstract":"<jats:p>Background: The use of neural stem cells (NSCs) to facilitate neurogenesis and improve impaired neural functions has attracted significant attention. Serine palmitoyltransferase long chain base subunit 2 (SPTLC2) induces apoptosis of neurons, while the mitogen-activated protein kinase (MEK)\/extracellular signal-regulated kinase (ERK) pathway promotes NSC differentiation and proliferation. This study investigated the roles of SPTLC2 and the MEK\/ERK pathway on the proliferation and metabolic activity of NSCs. Methods: SPTLC2 expression was altered through plasmid transfection and verified by Western blot and polymerase chain reaction (PCR) analyses. The effects of altered SPTLC2 expression on the metabolic activity and proliferation of NSCs were subsequently assessed using a cell counting kit and staining with 5-ethynyl-2'-deoxyuridine (EdU). Western blotting was used to examine the relationship between SPTLC2 and the MEK\/ERK pathway by investigating changes in protein expression. To determine whether SPTLC2 acts via the MEK\/ERK pathway, the activation state of this pathway was manipulated with U0126 and Erucin. Western blot and EdU staining were used to assess whether SPTLC2 affected the proliferation and metabolic activity of NSCs via the MEK\/ERK pathway. Results: Plasmid transfection led to significant changes in SPTLC2 expression at both the mRNA (p &lt; 0.01) and protein (p &lt; 0.05) levels. SPTLC2 overexpression significantly reduced the proliferation and metabolic activity of NSCs (p &lt; 0.05), whereas SPTLC2 knockdown mediated by siRNA significantly enhanced both parameters (p &lt; 0.05). Western blot analysis revealed that the ratios of p-MEK\/MEK and p-ERK\/ERK were inversely correlated with the expression level of SPTLC2 (p &lt; 0.05). Pharmacological modulation of the MEK\/ERK pathway significantly reversed the SPTLC2-induced changes in pathway activity (p &lt; 0.05) and partially restored the associated proliferative phenotypes. Conclusions: These findings indicate that SPTLC2 overexpression inhibits the proliferation and metabolic activity of NSCs, and that downregulation of SPTLC2 promotes these processes. The effects of SPTLC2 on NSCs were functionally associated with the MEK\/ERK pathway.<\/jats:p>","DOI":"10.31083\/jin52923","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:16:31Z","timestamp":1790698591000},"source":"Crossref","is-referenced-by-count":0,"title":["The Role of SPTLC2 and the MEK\/ERK Signaling Pathway in the Metabolic Activity and Proliferation of Neural Stem Cells"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0999-4740","authenticated-orcid":true,"given":"Tianqing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Longyan First Affiliated Hospital of Fujian Medical University, 364000 Longyan, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The 960th Hospital of the PLA Joint Logistics Support Force, 250031 Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folin","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Longyan First Affiliated Hospital of Fujian Medical University, 364000 Longyan, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Longyan First Affiliated Hospital of Fujian Medical University, 364000 Longyan, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xijing Hospital Affiliated to Air Force Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8705-8541","authenticated-orcid":true,"given":"Xinhong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Longyan First Affiliated Hospital of Fujian Medical University, 364000 Longyan, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Vieira MS, Santos AK, Vasconcellos R, Goulart VAM, Parreira RC, Kihara AH, et al. 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