Ask about this productRelated genes to: SLC6A8 Blocking Peptide
- Gene:
- SLC6A8 NIH gene
- Name:
- solute carrier family 6 member 8
- Previous symbol:
- -
- Synonyms:
- CRTR, CT1
- Chromosome:
- Xq28
- Locus Type:
- gene with protein product
- Date approved:
- 1994-12-19
- Date modifiied:
- 2016-02-17
Related products to: SLC6A8 Blocking Peptide
Related articles to: SLC6A8 Blocking Peptide
- Creatine deficiency syndromes (CDS) are rare neurometabolic disorders caused by defects in creatine biosynthesis (AGAT and GAMT deficiencies) or creatine transport (SLC6A8 deficiency). Early biochemical recognition is crucial for timely treatment of AGAT and GAMT deficiencies and for improving neurodevelopmental outcomes. In Morocco, expanding the liquid chromatography-tandem mass spectrometry (LC-MS/MS) biomarker panel for inherited metabolic disorders is a priority to strengthen diagnostic capacity and reduce diagnostic delay. We developed and validated a rapid LC-MS/MS method for the simultaneous quantification of creatine (Cr), guanidinoacetate (GAA), and creatinine (Crn) in plasma and urine using isotopically labelled internal standards and a standardized sample preparation procedure. Analytical performance, including linearity, precision, accuracy, sensitivity, matrix effects, carryover, inter-sample contamination, stability, and measurement uncertainty, was assessed in accordance with ISO 15189:2022 requirements. The assay showed excellent linearity across the analytical range (r > 0.99), with robust intra- and inter-day precision (CV < 10%). Limits of detection (LOD) were 0.05 µmol/L for Cr and 0.03 µmol/L for GAA in urine, and 0.05 µmol/L for Cr and GAA in plasma. The total run time was 1.1 min per sample, supporting high-throughput implementation. Method performance was further supported by satisfactory results in ERNDIM external quality assessment schemes. Preliminary internal reference ranges and expanded measurement uncertainty were calculated from the available anonymized dataset. This rapid LC-MS/MS method enables the measurement of key CDS biomarkers and contributes to expanding the LC-MS/MS biomarker panel for inherited metabolic disorders in Morocco. - Source: PubMed
Publication date: 2026/06/03
Meiouet FaïzaBoemer François - The creatine transporter (CRT/SLC6A8) plays a key role in cellular energy homeostasis, yet the molecular mechanism underlying creatine transport remains poorly understood. Here, we reconstruct the complete transport cycle of human CRT using a hybrid simulation strategy that combines constant-force steered molecular dynamics (cf-sMD) with targeted molecular dynamics (tMD). This approach captures continuous progression through the outward-open, outward-occluded, inward-occluded, and inward-open states and reveals a water-assisted, sequential intracellular release of Na2, creatine, and Na1. Hydration analysis shows that progressive water penetration into the binding pocket weakens protein-substrate and protein-ion interactions and destabilizes the bound state before release. Residue-level contact analysis identifies residues that interact with creatine along the transport pathway, while dynamic network analysis reveals a TM1-TM6 communication backbone that mediates long-range coupling during transport. Together, these results provide a molecular framework for creatine transport and establish an approach for investigating transport mechanisms across the broader solute carrier family. - Source: PubMed
Poudel PitambarPanday Shailesh KumarAlexov Emil - SLC6A8 encodes the creatine transporter (CRT), which mediates creatine transport across the plasma membrane in the brain, including the blood-brain barrier and neurons. Creatine transporter deficiency (CTD), caused by pathogenic variants in , leads to cerebral creatine depletion and cognitive impairment. Here, we investigated the developmental molecular mechanisms underlying CTD using the pathogenic c.1681G>C (G561R) variant of , which corresponds to a variant identified in in a patient with CTD. analyses using HEK293 cells expressing mutant mouse CRT carrying the G561R variant demonstrated impaired N-glycan maturation and plasma membrane localization of the transporter, resulting in markedly reduced creatine uptake, consistent with previous reports on the corresponding human CRT variant. To investigate the in vivo effects of this pathogenic variant, we generated CRT-G561R knock-in mice by introducing the c.1681G>C point mutation into the mouse gene using the CRISPR/Cas9 system. These male mice exhibited severe reductions in brain creatine levels, postnatal growth retardation, and impaired spatial memory, despite preserved gross brain morphology. Quantitative proteomic analyses of the hippocampus and cerebral cortex during postnatal development revealed region-dependent protein alterations in CTD. The hippocampus showed pronounced early postnatal remodeling involving proteins related to actin cytoskeleton organization and vesicle-mediated membrane trafficking, whereas the cerebral cortex exhibited a more gradual response involving creatine biosynthesis-related enzymes and later-emerging mitochondrial pathways, including the mitochondrial translation machinery. These findings demonstrate stage- and region-dependent proteomic remodeling during postnatal brain development in CTD. Creatine transporter deficiency (CTD) causes cerebral creatine depletion and intellectual disability; however, the developmental mechanisms linking creatine loss to brain dysfunction remain unclear. We performed developmental proteomic profiling of the hippocampus and cerebral cortex using a mouse model carrying a pathogenic variant identified in patients with CTD. Creatine transporter dysfunction induces distinct region- and stage-dependent molecular responses during postnatal brain maturation. The hippocampus shows early alterations in cytoskeleton-dependent membrane trafficking pathways, consistent with impaired synaptic and circuit maturation, whereas the cerebral cortex exhibits progressive metabolic and mitochondrial adaptations. These findings suggest that impaired creatine-dependent energy buffering disrupts distinct developmental programs across brain regions, potentially contributing to cognitive dysfunction by hindering early hippocampal circuit maturation. - Source: PubMed
Publication date: 2026/06/17
Ito ShingoIwata YumiUemura TatsukiSugimoto MichihikoKumabe HarukaMiyano AyakaNakamura TeruyaTashiro NaotoIeiri MegumuUmezaki MoekaChikamatsu ShomaMasuda TakeshiNakao SatohiroNakagata NaomiTakeo ToruAraki KimiOhtsuki Sumio - Creatine transporter 1 (CT1, SLC6A8) regulates cellular energy levels. Mutations in CT1 cause severe neurological disorders, whereas CT1 overexpression has been associated with cancer progression. Rational development of CT1 inhibitors has been limited by the absence of structural data. Here, we constructed homology models of CT1 representing distinct transport states and integrated them into a structure-based virtual screening workflow. From this approach, 16 top-ranked compounds were tested . Among them, compound showed inhibitory activity with an IC comparable to the reference ligand ompenaclid. We demonstrate that tiagabine () and its analogue also inhibit CT1. Following the completion of this study, cryo-EM structures of CT1 were reported. Retrospective comparison confirmed good agreement between our models and the experimental structures. These findings provide a computational-experimental framework for CT1 inhibitor discovery and support future structure-based drug design. - Source: PubMed
Publication date: 2026/05/06
Stary DorotaEl-Kasaby AliBoytsov DanilaZaręba PaulaGodyń JustynaMaszczyk MateuszRzepka ZuzannaWrześniok DorotaSotriffer ChristophSandtner WalterFreissmuth MichaelBajda Marek - Solute carrier family 6 member 8 (SLC6A8) is a Na- and Cl-dependent creatine transporter that mediates the transmembrane uptake of creatine, thereby sustaining intracellular creatine pools and cellular energy homeostasis. Dysregulated expression and function of SLC6A8 have been linked to creatine transporter deficiency (CTD), multiple malignancies, diabetes, obesity, and heart failure, underscoring its promising potential as a therapeutic target. Conventional creatine supplementation yields limited therapeutic benefit in the majority of CTD patients. Nevertheless, emerging strategies including gene therapy, small-molecule correctors, and lipophilic prodrug approaches have demonstrated preliminary efficacy in preclinical models of CTD. SLC6A8 is aberrantly expressed across numerous cancer types, and its inhibitor RGX-202 (also termed ompenaclid, chemically identified as β-GPA) exerts broad antitumor activity in preclinical models of colorectal cancer and hepatocellular carcinoma. This review summarizes recent advances delineating the involvement of SLC6A8 in neurological disorders, cancer, and other pathological conditions, with a particular emphasis on its translational potential as a therapeutic target. Clarifying the research status of SLC6A8 in various systemic diseases enables subsequent researchers to comprehensively understand its biological functions and clinical translational value from a more systematic perspective. - Source: PubMed
Publication date: 2026/06/15
Wang KaiLiu ChenjieHe JinkangXu MingmingLi LingjunLi Hongyang