|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Dysfunction of EAAT2 and accumulation of excessive extracellular glutamate has been implicated in the development of several neurodegenerative diseases including Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis.
|
21792905 |
2011 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
AQP4 depolarization may lead to motor neuron degeneration in ALS via GLT-1.
|
30980198 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Two alternative EAAT2 mRNA splice forms, one resulting from a partial retention of intron 7 (I7R), the other from a deletion of exon 9 (E9S), were previously implicated in the loss of EAAT2 protein in patients with amyotrophic lateral sclerosis.
|
15246112 |
2004 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Reduced expression and function of these transporters, especially EAAT2, has been reported in numerous neurological disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, schizophrenia and epilepsy.
|
25064045 |
2015 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
At end-stage disease, gliosis increased and EAAT2 loss in the ventral horn exceeded 90%, suggesting a role for this protein in the events leading to cell death in ALS.
|
11818550 |
2002 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
These results show that a loss of GLT-1 protein is not necessary for ALS-like neurodegeneration in G93A mice.
|
11790392 |
2002 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Therefore, we investigate the influence of the soluble factors released by hADSCs on the GLT1 in primary astrocytes cultured from SOD1(G93A) mice, a widely studied mutant human SOD1 transgenic model of ALS.
|
20152807 |
2010 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Mechanisms other than mutations within the coding region of EAAT2 must therefore be responsible for the low levels of EAAT2 seen in most cases of ALS.
|
10653305 |
1999 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
These findings suggest that VGluT2 and GLT-1 may be differentially involved in the pathogenesis of ALS via abnormal glutamate homeostasis at the presymptomatic stage and end stage of disease, respectively.
|
28526579 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
These results suggest that alternative splicing forms of GLT-1 mRNAs do not play a pathogenetic role in ALS but rather a physiological one in the normal spinal cord and brain.
|
9593515 |
1998 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
These findings suggest that the loss of EAAT2 in ALS is due to aberrant mRNA and that these aberrant mRNAs could result from RNA processing errors.
|
9539131 |
1998 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
It is implicated in amyotrophic lateral sclerosis (ALS, the most common type of motor neurone disease) where less EAAT2 is found, possibly involving aberrant intron 7 retention transcripts.
|
21569822 |
2011 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Activation of mGlu3 metabotropic glutamate receptors enhances GDNF and GLT-1 formation in the spinal cord and rescues motor neurons in the SOD-1 mouse model of amyotrophic lateral sclerosis.
|
25434487 |
2015 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
There was no quantitative change in mRNA for EAAT1, EAAT2, or EAAT3 in ALS motor cortex, even in patients with a large loss of EAAT2 protein (95% decrease compared with control) and decreased tissue glutamate transport (73% decrease compared with control).
|
8619555 |
1996 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Astrocyte elevated gene-1 is a novel regulator of astrogliosis and excitatory amino acid transporter-2 via interplaying with nuclear factor-κB signaling in astrocytes from amyotrophic lateral sclerosis mouse model with hSOD1<sup>G93A</sup> mutation.
|
29777762 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
DNA demethylation on selective CpG sites of the GLT1 promoter was highly correlated to increased GLT1 mRNA levels in astrocytes in response to neuronal stimulation; however, low level of methylation was found on CpG sites of EAAT2 promoter from postmortem motor cortex of human amyotrophic lateral sclerosis patients.
|
19672971 |
2010 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
CTD_human |
These findings indicate that the loss of GLT-1 protein in ALS mice selectively occurs in the areas affected by neurodegeneration and reactive astrocytosis and it is not associated with increases of glutamate levels in CSF.
|
11723166 |
2001 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
GeneticVariation
|
disease |
LHGDN |
Taken together, our findings suggest that caspase-3 cleavage of EAAT2 is one mechanism responsible for the impairment of glutamate uptake in mutant SOD1-linked ALS.
|
16567804 |
2006 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Further, reduced membralin and EAAT2 levels correlated with disease progression in spinal cord from SOD1-mutant mouse models, and reductions in membralin/EAAT2 were observed in human ALS spinal cord.
|
31112137 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis.
|
9585360 |
1998 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
The mutation did not affect normal EAAT2 function nor non-ALS mice.
|
28342750 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
The implication of this study for the mechanisms of EAAT2 protein loss in ALS and AD is discussed.
|
12504589 |
2002 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, the extent of sumoylation of EAAT2 does not change during the course of ALS in the SOD1-G93A mouse and is not affected by the expression of ALS-causative mutant SOD1 proteins in astrocytes in vitro, indicating that EAAT2 sumoylation is not driven by pathogenic mechanisms.
|
24753081 |
2014 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
GLT-1 dysregulation occurs in various neurological diseases including Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and epilepsy.
|
31338020 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.400 |
Biomarker
|
disease |
BEFREE |
Inhibiting miR-218 with antisense oligonucleotides in amyotrophic lateral sclerosis model mice mitigates the loss of EAAT2 and other miR-218-mediated changes, providing an important in vivo demonstration of the relevance of microRNA-mediated communication between neurons and astrocytes.
|
30007309 |
2018 |