Ask about this productRelated genes to: SLC41A1 Blocking Peptide
- Gene:
- SLC41A1 NIH gene
- Name:
- solute carrier family 41 member 1
- Previous symbol:
- -
- Synonyms:
- MgtE
- Chromosome:
- 1q32.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-02-26
- Date modifiied:
- 2016-02-17
Related products to: SLC41A1 Blocking Peptide
Related articles to: SLC41A1 Blocking Peptide
- : Neuropsychiatric disorders such as Alzheimer's disease (AD), bipolar disorder (BD), and depression exhibit shared glutamatergic abnormalities, although their upstream molecular mechanisms remain poorly defined. Magnesium (Mg) serves as a key regulator of N-methyl-D-aspartate (NMDA) receptor function; however, the role of Mg transporters, particularly SLC41A1, has not been systematically investigated. As NMDA receptor dysregulation contributes to emotional and cognitive impairments, elucidating Mg-NMDA signaling may enable the development of novel therapeutic strategies. : We integrated Mendelian randomization, locus colocalization, human brain transcriptomics, functional enrichment, and co-expression analyses to determine whether SLC41A1 functions as a cross-disorder molecular driver. In addition, in vitro electrophysiological experiments using field potential recordings in hippocampal Schaffer-CA1 synapses were conducted to validate its functional role in NMDA receptor-mediated synaptic transmission. : Genetically elevated SLC41A1 expression increased the risk of AD, BD, depression, and alcohol dependence, with strong colocalization analyses supporting shared causal variants. Transcriptomic profiling revealed SLC41A1 upregulation in AD and BD, with enrichment in magnesium transport, mitochondrial function, and synaptic signaling pathways. Co-expression networks across GTEx brain regions demonstrated strong correlations with NMDA-related genes (e.g., , , ). Under NMDAR-selective recording conditions, both imipramine treatment and SLC41A1 knockdown significantly reduced NMDAR-mediated fEPSP amplitudes, supporting a role for SLC41A1 in regulating NMDA receptor-dependent synaptic responses. : This study identifies SLC41A1 as a magnesium-centered, transdiagnostic therapeutic target that links Mg homeostasis to NMDA-dependent synaptic dysfunction. These findings provide a mechanistic foundation for developing SLC41A1-modulating or magnesium-based therapeutic approaches for mood and cognitive disorders. - Source: PubMed
Publication date: 2026/03/09
Chen XinruDeng WenhaoChen XinruiYu Yang - Magnesium ion (Mg), particularly its free intracellular form, is indispensable for regulating diverse cellular functions. This critical role implies the existence of dedicated transporters and channels in the plasma membrane that coordinate Mg uptake, intracellular storage, and efflux to maintain homeostasis. Although numerous molecular entities responsible for such Mg transport have been reported over the past decades, there is still limited knowledge of their precise functions and disease implications. This review focuses on the solute carrier family 41 (SLC41), which consists of three isoforms (A1, A2, and A3) that share homology with the prokaryotic magnesium transporter E (MgtE) Mg transporter family. Accumulating evidence has established SLC41A1 as the Na/Mg exchanger-a predominant Mg-efflux system. By contrast, the subcellular site of SLC41A2-mediated Mg flux remains undefined, with potential roles at either the plasma membrane or organellar membranes, and SLC41A3 facilitates Na-dependent Mg efflux from mitochondria. Additionally, several studies have reported the association between SLC41s and diseases, including Parkinson's disease, hepatocellular carcinoma, and nephronophthisis-related ciliopathies. By synthesizing current knowledge, this review aims to enhance the understanding of SLC41 transporters in health and disease and to explore their potential as therapeutic targets for clinical intervention. - Source: PubMed
Publication date: 2026/02/09
Cao YuRao CaijunDu Zhipeng - The tumor microenvironment (TME) fosters immunosuppression and T-cell exhaustion, which limit the efficacy of immunotherapy. Magnesium ions (Mg) have recently been identified as potent immunomodulators that enhance cytotoxic T lymphocyte (CD8 T) activity. However, conventional carriers for Mg delivery suffer from poor biocompatibility and inefficient targeting, restricting therapeutic outcomes. In this study, we developed an engineered extracellular vesicle (EV)-based system for targeted Mg delivery. Dendritic cells were genetically modified to overexpress magnesium-specific channel protein MgtE (SLC41A1), enabling efficient Mg encapsulation into dendritic cell-derived EVs (E-DEVs). The resulting Mg-loaded vesicles (E-DEVs@Mg) displayed strong tropism toward tumor-draining lymph nodes (TDLNs) and effectively modulated T-cell metabolism. Mechanistic studies revealed that E-DEVs@Mg enhanced glycolysis and oxidative phosphorylation, restoring the metabolic fitness of exhausted CD8 T cells. When combined with immune checkpoint blockade therapy, this strategy achieved a synergistic tumor suppression. Our findings highlight engineered DEVs as a biocompatible and effective Mg delivery platform, providing a promising approach for metabolic reprogramming and improved cancer immunotherapy. - Source: PubMed
Publication date: 2025/11/25
Yu XiaoyuChen ShuqiSun RongYao ChenluWu BingbingWang HengWeng ChenhuiSun DongdongWang ChaoXu Fang - Although regenerative endodontics demonstrate promise for dental pulp regeneration, chronic inflammation often hinders the success. This study aims to explore the mechanism whereby lipopolysaccharide (LPS) induces dental pulp regeneration failure. Transcriptomic profiling of LPS-stimulated dental pulp stem cells (DPSCs) reveals dysregulated cation homeostasis and increased magnesium (Mg⁺) transmembrane transport. Mechanistically, LPS is observed to activate the transcription factor signal transducer and activator of transcription 5A (STAT5A), which binds to the solute carrier family 41 member 1 (SLC41A1) promoter, thereby upregulating the Mg⁺ efflux transporter and depleting intracellular Mg⁺ levels. Mg⁺ efflux destabilizes the mitochondrial permeability transition pore (mPTP), thus facilitating its opening via the interaction of oligomycin sensitivity-conferring protein (OSCP) and cyclophilin D (CypD), which releases reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) and exacerbates oxidative stress. The released mtDNA activates the absent in melanoma 2 (AIM2) inflammasome, thereby amplifying gasdermin D (GSDMD)-mediated pyroptosis. Exogenous supplementation with Mg⁺ restores intracellular Mg⁺ homeostasis, suppresses mPTP opening, and reduces mtDNA and ROS leakage, thereby rescuing DPSCs viability and differentiation capacity. This study identifies SLC41A1-mediated Mg⁺ dysregulation as a pivotal driver of LPS-induced mitochondrial damage and demonstrates that Mg⁺ replenishment is a therapeutic strategy to counteract inflammation-driven regenerative failure. - Source: PubMed
Publication date: 2025/08/19
Liu YuanSong ChenyuZhang LiyuanHan XueLi ChaoyuanYan YanhongXing LudanSi MengtingYang BoCheng LingyuanMuramatsu AkimiJiang Beizhan - The kidneys play a pivotal role in the reabsorption of Mg within the human body. However, the precise functions of Mg and its transporters in the context of kidney renal clear cell carcinoma (KIRC) remain limited. In an effort to address this, we have employed bioinformatics analysis of the TCGA database to devise a novel scoring system, termed the Mg score, which we have used to establish a diagnosis and prognostication framework for KIRC. This score is predicated on the expression levels of nine Mg transporters. It was established that low expression of Mg transporters, including TRPM7, SLC41A1, MRS2, MAGT1, CNNM2, CNNM3, and CNNM4, is linked to a poor prognosis in KIRC. We observed that the expression levels of TRPM7, SLC41A1, MRS2, MAGT1, CNNM2, and CNNM3 were significantly reduced in advanced-stage KIRC patients compared to those in early-stage patients. CNNM3 knockdown promoted the proliferation and migration of KIRC cells in vitro, and interestingly, this effect was accompanied by an increase in both intracellular free Mg and Fe. Exogenous Mg supplementation has been shown to further sensitize KIRC cells to ferroptosis, under both basal conditions and in the presence of CNNM3 knockdown, with a significant enhancement of lipid peroxidation and ferroptosis being observed. At the subcellular level, CNNM3 knockdown has been shown to exacerbate RSL3-induced mitochondrial damage and mitochondrial ROS production. The study thus identifies a potential "Mg-Fe" homeostatic mechanism in KIRC cells, with CNNM3 serving as a critical regulatory component. The findings of the present study offer a new direction for further research, with the potential to develop novel and effective therapeutic strategies for KIRC patients exhibiting CNNM3 low expression and unfavorable clinical outcomes. The therapeutic targeting of ferroptosis may present a viable treatment approach for patients with KIRC who exhibit low CNNM3 expression and poor clinical outcomes. - Source: PubMed
Hua SiqiYang ChunhaoShang PengyouZhan MingjieLi KaiqiangZhang TaoJia YanlongHua ZichunZhu Bo