Ask about this productRelated genes to: SPTLC1 Blocking Peptide
- Gene:
- SPTLC1 NIH gene
- Name:
- serine palmitoyltransferase long chain base subunit 1
- Previous symbol:
- HSN1
- Synonyms:
- LCB1, SPTI, HSAN1, hLCB1
- Chromosome:
- 9q22.31
- Locus Type:
- gene with protein product
- Date approved:
- 2000-07-31
- Date modifiied:
- 2019-04-23
Related products to: SPTLC1 Blocking Peptide
Related articles to: SPTLC1 Blocking Peptide
- Coffin-Siris syndrome (CSS) is predominantly attributed to variants in ARID1B gene, however, the molecular pathways connecting ARID1B to myelination and neural development are not well elucidated. - Source: PubMed
Publication date: 2026/04/10
Yang XingkunGan ZhongzhiZhou YasiZhang MingmingWu ShuijuanHe FeiShen ZongruiMa ShunfeiSu XiXiong Fu - Parkinson's disease (PD) is characterized by advanced neuronal degeneration, mitochondrial impairment, and aberrant lipid metabolism. Emerging evidence suggests that dysregulated sphingolipid biosynthesis, particularly through the upregulation of serine palmitoyltransferase (SPTLC1), contributes to the pathogenesis of PD. This study investigates the neuroprotective potential of Zanthoxylum armatum essential oil (ZAEO) in an MPP-induced SH-SY5Y cell model of PD, focusing on modulation of SPTLC1 expression and associated neurotoxicity. GC-MS (Gas Chromatography-Mass Spectroscopy) analysis identified 28 phytoconstituents in ZAEO, accounting for 99.9% of its composition, with linalool (66.74%) and limonene (17.78%) as the principal components. ZAEO treatment significantly attenuated MPP-induced cytotoxicity, restored neuronal nuclear marker NeuN (Neuronal nuclei), and notably suppressed the overexpression of SPTLC1, a key enzyme driving ceramide accumulation and mitochondrial stress in PD pathology. Immunofluorescence and cell viability assays corroborated these protective effects. Furthermore, molecular docking of ZAEO constituents with SPTLC1 (PDB ID: 7K0K) revealed high-affinity binding of minor compounds, including phellandral, humulene, and (-)-carvone, suggesting direct interactions with the enzyme and potential inhibition. These findings underscore the ability of ZAEO to mitigate neurodegeneration by modulating the sphingolipid axis and support its development as a multi-targeted phytotherapeutic strategy for Parkinson's disease. - Source: PubMed
P KrishnaPancholi BhaskaranandGarabadu DebapriyaSharma PriyankaThareja Suresh - This study aimed to investigate the mechanisms by which Acanthopanax senticosus extract(ASH) exerts effects on α-synuclein(α-syn) overexpressing transgenic mouse model of Parkinson's disease(PD), with a focus on its regulation of brain lipid metabolism. Twenty PD model mice were randomly assigned to a model group or an ASH treatment group(45.5 mg·kg~(-1) by gavage for 4 weeks), and 10 C57BL/6 mice served as a normal control group. Behavioral assessments revealed that, compared with controls, PD model mice showed prolonged pole test time, reduced spontaneous locomotor activity, shorter latency to fall in the rotarod test, and decreased total distance traveled in the open field test. Serum levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), caspase-9 were significantly elevated, B-cell lymphoma-2(Bcl-2), and proliferating cell nuclear antigen(PCNA) expression was reduced, and marked neuronal damage was observed in brain tissue. ASH intervention significantly improved these behavioral and biochemical parameters and attenuated neuronal injury. Untargeted lipidomics analysis revealed significant alterations in sphingomyelin(SM), ceramide(Cer), phosphatidylcholine(PC), and phosphatidylserine(PS) across multiple brain regions(cortex, substantia nigra, cerebellum, and striatum) in PD mice, which were notably restored by ASH treatment. Pathway analysis indicated that these metabolites were predominantly involved in sphingolipid metabolism. Western blot further demonstrated that ASH downregulated the expression of key sphingolipid metabolic enzymes serine palmitoyltransferase long-chain base subunits 1 and 2(SPTLC1 and SPTLC2) and upregulated UDP-glucose ceramide glucosyltransferase(UGCG), β-galactosylceramidase(GALC), and sphingosine kinase 2(SPHK2), thereby suppressing abnormal SM and Cer accumulation in the substantia nigra and elevating PS and PC levels in the striatum. Spearman's correlation analysis supported the modulatory effect of ASH on brain lipid metabolic profiles. In conclusion, ASH improves behavioral deficits, exerts anti-inflammatory effects, and regulates sphingolipid metabolism to correct disordered lipid profiles, thereby providing neuroprotective effects in PD mice. - Source: PubMed
Gao AoXu Xiao-MinLu Ning-XiaYu Dong-HuaWang YuChen Ping-PingLu FangLiu Shu-Min - ORMDL proteins are essential negative regulators of the serine palmitoyltransferase (SPT) complex, thereby controlling the rate of de novo sphingolipid synthesis. Although mammalian ORMDLs undergo rapid turnover, the mechanisms regulating their stability remain unclear, with conflicting observations across studies. Here, we combined lipidomics, proteomics, and biochemical assays to investigate ORMDL regulation in HEK293, RPE-1, and primary mouse bone marrow-derived mast cells (BMMCs). Inhibition of SPT by myriocin or of ceramide synthases by fumonisin B (FB) profoundly altered sphingolipid composition but induced minimal global proteomic changes while consistently reducing ORMDL protein levels. In contrast, overexpression of a single-chain SPT increased ORMDLs alongside elevated sphingolipids, an effect reversed by myriocin or FB. ORMDL loss closely correlated with ceramide depletion and, in HEK293 and RPE-1 cells, was prevented by proteasome inhibition, whereas autophagy inhibition had no effect. In BMMCs, both pathways contributed to ORMDL regulation, consistent with high basal autophagy reflected by elevated LC3-II. The p97/valosin-containing protein ATPase was involved in the regulation of ORMDL turnover in all tested cell lines. Mutation of conserved asparagines (N11/N13) in ORMDL3, which mediate ceramide binding and stabilization of the inhibitory conformation, disrupted association with SPTLC1 and SPTLC2, mimicking myriocin-induced complex dissociation, while FB had a weaker effect. Together, these findings suggest that ceramide depletion is the primary trigger for ORMDL degradation in HEK293, RPE-1, and BMMCs and reveal a proteasome-dependent pathway that can be supplemented by autophagy in cells with high basal autophagic activity. - Source: PubMed
Mrkacek MichalTumova MagdaPuskasu AlexUtekal PavolVrbacky MarekKuchar LadislavDraber PetrBugajev Viktor - Bone loss-related disorders, driven by impaired osteoblast activity, pose a growing global health challenge, yet current anabolic therapies remain limited due to an incomplete understanding of osteoblast dysfunction. Emerging evidence suggests that lactate-derived lysine lactylation-a glycolysis-linked PTM-may regulate osteoblast differentiation and bone homeostasis, though its landscape and functional impact in osteoblasts are largely unknown. Here, we integrated multi-omics profiling, Mendelian randomization (MR), and computational modeling to investigate lactylation-mediated osteogenic regulation. Using osteoblast models, we mapped dynamic proteomic and lactylome changes during differentiation, identifying 43 key proteins with concurrent alterations in expression and lactylation. Integrated MR analysis of human genetic data identified NANS and SPTLC1 as causal regulators of bone mineral density. Molecular dynamics simulations revealed lactylation-driven functional remodeling of these proteins, and network pharmacology suggested FDA-approved compounds (e.g., Suramin sodium and Paritaprevir) as potential osteogenic agents. This study advances mechanistic understanding of osteogenesis and provides a framework for discovering small molecules that mimic lactylation-induced conformational changes for drug repurposing in clinical applications. - Source: PubMed
Publication date: 2026/02/06
Chen RuijingGe SiliangChang FeifanChen MingLi YiLi YihuiYou DeshengTang PeifuYin Pengbin