In:
The FEBS Journal, Wiley, Vol. 280, No. 23 ( 2013-12), p. 6114-6127
Abstract:
Glutamate‐induced excitotoxicity is involved in many neurological diseases. Preso, a novel postsynaptic scaffold protein, mediates excitatory synaptic transmission and various synaptic functions. In this study, we investigated the role of Preso in the regulation of glutamate‐induced excitotoxicity in rat cortical neurons. Knockdown of Preso with small interfering RNA improved neuronal viability and attenuated the elevation of lactate dehydrogenase ( LDH ) release after glutamate treatment. Downregulation of Preso also inhibited an increase in the BAX / B cl‐2 ratio and cleavage of caspase‐9 and caspase‐3. Although the expression and distribution of metabotropic glutamate receptor (m G lu R ) 1/5, NR 1, NR 2 A and NR 2 B were not changed by knockdown of P reso, downregulation of P reso protected neurons from glutamate‐induced excitotoxicity by inhibiting m G lu R and N ‐methyl‐ d ‐aspartate receptor function. However, downregulation of P reso neither affected the expression of G lu R 1 and G lu R 2 nor influenced the function of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate receptor after glutamate treatment. Furthermore, intracellular C a 2+ was an important downstream effector of P reso in the regulation of excitotoxicity. These results suggest that expression of P reso promotes the induction of excitotoxicity by facilitating different glutamate receptor signaling pathways. Therefore, P reso might be a potential pharmacological target for preventing and treating neurological diseases.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2013.280.issue-23
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2172518-4
SSG:
12
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