|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study we addressed the effect of CYP46A1 on NMDAR-mediated excitotoxicity in HD primary neurons and its role in modulating cholesterol and localization of GLUN2B in lipid rafts.
|
30107216 |
2018 |
|
Huntington Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Although the activation of extrasynaptic GluN2B-containing N-methyl-d-aspartate (NMDA) receptors has been implicated in neurodegenerative diseases, such as Alzheimer's and Huntington's disease, their physiological function remains unknown.
|
30110236 |
2018 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Previous studies have shown enhanced N-methyl-d-aspartate (NMDA)-induced excitotoxicity in neuronal models of HD, mediated in part by increased NMDA receptor (NMDAR) GluN2B subunit binding with the postsynaptic density protein-95 (PSD-95).
|
22198502 |
2012 |
|
Huntington Disease
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Because of the known role of the GRIN2B C2664T polymorphism in HD neuropathology, which is partly due to increased glutamatergic neural transmission, we analyze how this polymorphism influences error processing and response inhibition in a sample of healthy probands (N=65).
|
20399867 |
2010 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
This is the first direct in vivo evidence of NR2B-NMDAR-mediated excitotoxicity in the context of HD.
|
19279257 |
2009 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Treatment of cultured MSNs with Tat-NR2B9c peptide blocked binding of NR2B with SAP102 and PSD-95 and reduced NMDAR surface expression by 20% in both YAC transgenic and wild-type MSNs, and also restored susceptibility to NMDAR excitoxicity in YAC HD MSNs to levels observed in wild-type MSNs; a similar effect on excitotoxicity was observed after knockdown of PSD-95 by small interfering RNA.
|
19726651 |
2009 |
|
Huntington Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Other lines of investigation suggest that expression of mutant Htt facilitates activity of the NR2B subtype of NMDA receptors and the type 1 inositol 1,4,5-trisphosphate receptors (InsP(3)R1), and that disturbed calcium (Ca(2+)) signaling causes apoptosis of MSNs in HD.
|
18502655 |
2008 |
|
Huntington Disease
|
0.100 |
GeneticVariation
|
disease |
LHGDN |
In order to expand these findings we fine-mapped a larger HD patient panel (n = 250) using densely spaced markers flanking the originally associated SNPs in GRIN2A and GRIN2B.
|
17569088 |
2007 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
In order to expand these findings we fine-mapped a larger HD patient panel (n = 250) using densely spaced markers flanking the originally associated SNPs in GRIN2A and GRIN2B.
|
17569088 |
2007 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
LHGDN |
We conclude that these two genes, coding for NR2B and NR2A subtypes mainly expressed in the striatum, may influence the variability in AO of HD.
|
15742215 |
2005 |
|
Huntington Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We conclude that these two genes, coding for NR2B and NR2A subtypes mainly expressed in the striatum, may influence the variability in AO of HD.
|
15742215 |
2005 |
|
Huntington Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Together with previous results, our data suggest that enhanced activity of NR2B-containing NMDARs is one of the earliest changes leading to neuronal degeneration in HD.
|
15240759 |
2004 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Experimental evidence indicates that (1) Ca2+ homeostasis is abnormal in mitochondria isolated from lymphoblasts of HD patients and from brains of the YAC72 HD mouse model; (2) Httexp leads to potentiation of NR1/NR2B NMDA receptor activity in heterologous expression systems and in MSN from YAC72 HD mouse model; and (3) Httexp binds to the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) carboxy-terminus and causes sensitization of InsP3R1 to activation by InsP3 in planar lipid bilayers and in MSN.
|
15336977 |
2004 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our data support a role for NR2B-subtype NMDAR activation as a trigger for selective neuronal degeneration in HD.
|
11906693 |
2002 |
|
Huntington Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
Since NR1A/NR2B is the predominant NMDAR subtype in neostriatal medium-sized spiny neurons, enhancement of NMDA-induced apoptotic death in NR1A/NR2B-expressing cells by full-length mutant htt may contribute to selective neurodegeneration in HD.
|
11161468 |
2001 |
|
Huntington Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Changes of NMDA receptor subunit (NR1, NR2B) and glutamate transporter (GLT1) mRNA expression in Huntington's disease--an in situ hybridization study.
|
9100675 |
1997 |