更新于：2024-11-01

GLUT1 x GluN1

更新于：2024-11-01

基本信息

关联

项与 GLUT1 x GluN1 相关的药物

WZB117

靶点

GLUT1 x GluN1

作用机制

GLUT1抑制剂 [+1]

在研机构

The Ohio University

原研机构

The Ohio University

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GLUT1 x GluN1 相关的临床结果

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100 项与 GLUT1 x GluN1 相关的转化医学

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0 项与 GLUT1 x GluN1 相关的专利（医药）

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项与 GLUT1 x GluN1 相关的文献（医药）

2021-12-01·Journal of Pharmaceutical Sciences3区 · 医学

Systemic Inflammation Induced Changes in Protein Expression of ABC Transporters and Ionotropic Glutamate Receptor Subunit 1 in the Cerebral Cortex of Familial Alzheimer`s Disease Mouse Model

3区 · 医学

Article

作者: Mikko Gynther ; Elena Puris ; Paula Korhonen ; Jari Koistinaho ; Tarja Malm ; Sanna Loppi ; Seppo Auriola ; Katja M. Kanninen

Alzheimer's disease (AD) is an incurable disease, with complex pathophysiology and a myriad of proteins involved in its development. In this study, we applied quantitative targeted absolute proteomic analysis for investigation of changes in potential AD drug targets, biomarkers, and transporters in cerebral cortices of lipopolysaccharide (LPS)-induced neuroinflammation mouse model, familial AD mice (APdE9) with and without LPS treatment as compared to age-matched wild type (WT) mice. The ABCB1, ABCG2 and GluN1 protein expression ratios between LPS treated APdE9 and WT control mice were 0.58 (95% CI 0.44-0.72), 0.65 (95% CI 0.53-0.77) and 0.61 (95% CI 0.52-0.69), respectively. The protein expression levels of other proteins such as MGLL, COX-2, CytC, ABCC1, ABCC4, SLC2A1 and SLC7A5 did not differ between the study groups. Overall, the study revealed that systemic inflammation can alter ABCB1 and ABCG2 protein expression in brain in AD, which can affect intra-brain drug distribution and play a role in AD development. Moreover, the inflammatory insult caused by peripheral infection in AD may be important factor triggering changes in GluN1 protein expression. However, more studies need to be performed in order to confirm these findings. The quantitative information about the expression of selected proteins provides important knowledge, which may help in the optimal use of the mouse models in AD drug development and better translation of preclinical data to humans.

2020-05-01·Annals of Neurology1区 · 医学

N‐Methyl‐D‐Aspartate Receptor Antibodies in Autoimmune Encephalopathy Alter Oligodendrocyte Function

1区 · 医学

Article

作者: Barman, Sumanta ; Dalmau, Josep ; Goebels, Norbert ; Serrano‐Regal, María Paz ; Matute, Carlos ; Domercq, María ; Palma, Ana ; Maudes, Estibaliz ; Sánchez‐Gómez, María Victoria

ObjectiveAntibodies against neuronal N‐methyl‐D‐aspartate receptors (NMDARs) in patients with anti‐NMDAR encephalitis alter neuronal synaptic function and plasticity, but the effects on other cells of the nervous system are unknown.MethodsCerebrospinal fluid (CSF) of patients with anti‐NMDAR encephalitis (preabsorbed or not with GluN1) and a human NMDAR‐specific monoclonal antibody (SSM5) derived from plasma cells of a patient, along the corresponding controls, were used in the studies. To evaluate the activity of oligodendrocyte NMDARs and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in vitro after exposure to patients' CSF antibodies or SSM5, we used a functional assay based on cytosolic Ca2+ imaging. Expression of the glucose transporter (GLUT1) in oligodendrocytes was assessed by immunocytochemistry.ResultsNMDAR agonist responses were robustly reduced after preincubation of oligodendrocytes with patients' CSF or SSM5 but remained largely unaltered with the corresponding controls. These effects were NMDAR specific, as patients' CSF did not alter responses to AMPA receptor agonists and was abrogated by preabsorption of CSF with HEK cells expressing GluN1 subunit. Patients' CSF also reduced oligodendrocyte expression of glucose transporter GLUT1 induced by NMDAR activity.InterpretationAntibodies from patients with anti‐NMDAR encephalitis specifically alter the function of NMDARs in oligodendrocytes, causing a decrease of expression of GLUT1. Considering that normal GLUT1 expression in oligodendrocytes and myelin is needed to metabolically support axonal function, the findings suggest a link between antibody‐mediated dysfunction of NMDARs in oligodendrocytes and the white matter alterations reported in patients with this disorder. ANN NEUROL 2020;87:670–676

2016-08-01·Neurochemical Research3区 · 医学

Peripheral Levels of AGEs and Astrocyte Alterations in the Hippocampus of STZ-Diabetic Rats

3区 · 医学

Article

作者: Batassini, Cristiane ; Hansen, Fernanda ; Gonçalves, Carlos-Alberto ; Sesterheim, Patrícia ; Zanotto, Caroline ; Nardin, Patrícia ; Gasparin, Manuela Sangalli

Diabetic patients and streptozotocin (STZ)-induced diabetes mellitus (DM) models exhibit signals of brain dysfunction, evidenced by neuronal damage and memory impairment. Astrocytes surrounding capillaries and synapses modulate many brain activities that are connected to neuronal function, such as nutrient flux and glutamatergic neurotransmission. As such, cognitive changes observed in diabetic patients and experimental models could be related to astroglial alterations. Herein, we investigate specific astrocyte changes in the rat hippocampus in a model of DM induced by STZ, particularly looking at glial fibrillary acidic protein (GFAP), S100B protein and glutamate uptake, as well as the content of advanced glycated end products (AGEs) in serum and cerebrospinal fluid (CSF), as a consequence of elevated hyperglycemia and the content of receptor for AGEs in the hippocampus. We found clear peripheral alterations, including hyperglycemia, low levels of proinsulin C-peptide, elevated levels of AGEs in serum and CSF, as well as an increase in RAGE in hippocampal tissue. We found specific astroglial abnormalities in this brain region, such as reduced S100B content, reduced glutamate uptake and increased S100B secretion, which were not accompanied by changes in GFAP. We also observed an increase in the glucose transporter, GLUT-1. All these changes may result from RAGE-induced inflammation; these astroglial alterations together with the reduced content of GluN1, a subunit of the NMDA receptor, in the hippocampus may be associated with the impairment of glutamatergic communication in diabetic rats. These findings contribute to understanding the cognitive deficits in diabetic patients and experimental models.