Postsynaptic density protein-95 (PSD-95)/Discs-large/ZO-1 (PDZ) domains play an essential role in the regulation of intracellular signaling involved in neuronal disease and cancer. Tat-NR2B9c is a 20-mer peptide consisting of nine C-terminal amino acids of the NMDA NR2B subunit. It inhibits PSD-95 domain 1 and PSD-95 domain 2 with EC50 values of 670 nM and 6.7 nM, respectively. The IC50 values for Tat-NR2B9c inhibiting the interactions between NMDAR2A, NMDAR2B, NMDAR2C and PSD-95 are 0.5, 8, and 0.75μm, respectively. Tat-NR2B9c also inhibits the interaction between neuronal nitric oxide synthase and PSD-95 with an IC50 value of 0.2μm[3]. In NMDA-treated neuronal cultures, Tat-NR2B9c at 0.5µM suppressed NMDA-induced superoxide production by 75%. The NMDA-type glutamate receptor-triggered NOX2 activation and DNA damage were also prevented by Tat-NR2B9c at 0.5µM[4]. In mice subjected to temporary middle cerebral artery occlusion (tMCAO) for 30 and 60 min, treatment with 10nmol/g Tat-NR2B9c significantly decreased infarct volumes by 24.5% and 26.0%, respectively[5].
Tat-NR2B9c 细胞实验
Cell Line
Concentration
Treated Time
Description
References
AtT20 cells
2 µM
1 hour
TAT-NR2B9c did not affect NMDAR-dependent death of NR-AtT20 cells.
J Neurosci. 2008 Oct 15;28(42):10696-710.
YAC128 MSNs
200 nM
1 hour
Reduced the binding of NR2B with PSD-95 and SAP102
J Neurosci. 2009 Sep 2;29(35):10928-38.
neuronal cultures
0.5 μM
30 min
Tat-NR2B9c suppressed NMDA-induced superoxide production by about 75%
J Cereb Blood Flow Metab. 2015 May;35(5):739-42.
rat cortical neurons
0.5 μM
24 h
To investigate the effect of Tat-NR2B9c on the interaction of PSD95 with NR2B-nNOS or neurexin-1-neuroligin-1, it was found that Tat-NR2B9c significantly reduced the formation of the PSD95-NR2B-nNOS complex and promoted the formation of the neurexin-1-neuroligin-1-PSD95 complex.
Blocked binding of NR2B with SAP102 and PSD-95 and reduced NMDAR surface expression by 20%
J Neurosci. 2009 Sep 2;29(35):10928-38.
Cortical neurons
2 µM
1 hour
TAT-NR2B9c significantly reduced excitotoxic neuronal death and p38-mediated ischemic damage, without impairing an NMDAR-dependent plasticity model or prosurvival signaling to CREB or Akt.
J Neurosci. 2008 Oct 15;28(42):10696-710.
Tat-NR2B9c 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rat
Nerve injury-induced pain model
Intrathecal injection
125 ng
Single injection, lasting 5 hours
Tat-NR2B9c attenuates nerve injury-induced mechanical and cold hypersensitivity by disrupting the interaction between PSD-95 and NR2B subunits, without affecting locomotor performance.
Mol Ther. 2011 Oct;19(10):1780-92
Mice
Temporary middle cerebral artery occlusion (tMCAO) model
Intravenous injection
10 nM/g
Single dose, over 5 minutes
To evaluate the neuroprotective effect of Tat-NR2B9c in the tMCAO model in mice, results showed that a dose of 10 nMole/g significantly reduced infarct volume
J Cereb Blood Flow Metab. 2016 Mar;36(3):555-61
Rats
Intracerebral hemorrhage model
Tail vein injection
2.6 mg/kg
Once every 3 days until the end of the experiment
To investigate the rescue effect of Tat-NR2B9c on secondary brain injury induced by intracerebral hemorrhage, it was found that Tat-NR2B9c significantly reduced neuronal death and degeneration, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats.
TAT-NR2B9c reduced p38-mediated ischemic damage, and synergized with JNK inhibitors to ameliorate severe excitotoxic neuronal loss in vitro and ischemic cortical damage in vivo.
J Neurosci. 2008 Oct 15;28(42):10696-710.
Rats
Focal stroke model
Tail vein injection
3 nmol/g
Single dose, 5 minutes before ischemia
To evaluate the neuroprotective effects of Tat-NR2B9c after cerebral ischemia. Results showed that Tat-NR2B9c significantly improved the recovery of cortical function after stroke, evidenced by greater recovery of fEPs and EEG power.
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