当前位置： SCI文献检索 > Progress in Brain Research期刊下所有文献 > Assemblies of glutamate receptor subunits with post-synaptic density proteins and their alterations in Parkinson's disease.

Assemblies of glutamate receptor subunits with post-synaptic density proteins and their alterations in Parkinson's disease.

Abstract：

:N-methyl-D-aspartate (NMDA) receptors have been implicated as a mediator of neuronal injury associated with many neurological disorders including ischemia, epilepsy, brain trauma, dementia and neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease. To this, non-selective NMDA receptor antagonists have been tried and have been shown to be effective in many experimental animal models of disease, and some of these compounds have moved into clinical trials. However, the initial enthusiasm for this approach has waned, because the therapeutic index for most NMDA antagonists is quite poor, with significant adverse effects at clinically effective doses, thus limiting their utility. More recently, the concept that the exact pathways downstream NMDA receptor activation could represent a key variable element among neurological disorders has been put forward. In particular, variations in NMDA receptor subunit composition could be important in different disorders, both in the pathophysiological mechanisms of cell death and in the application of specific symptomatic therapies. As to PD, NMDA receptor complex has been shown to be altered in experimental models of parkinsonism and in PD in humans. Further, it has become increasingly evident that the NMDA receptor complex is intimately involved in the regulation of corticostriatal long-term potentiation, which is altered in experimental parkinsonism. The following sections will examine the modifications of specific NMDA receptor subunits as well as post-synaptic associated signalling complex including kinases and scaffolding proteins in experimental parkinsonism. These findings may allow the identification of specific molecular targets whose pharmacological or genetic manipulation might lead to innovative therapies for PD.

journal_name

Prog Brain Res

journal_title

Progress in brain research

authors

Gardoni F,Ghiglieri V,Di Luca M,Calabresi P

doi

10.1016/S0079-6123(10)83009-2

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

169-82

eissn

0079-6123

issn

1875-7855

pii

S0079-6123(10)83009-2

journal_volume

183

pub_type

杂志文章,评审

在线工具

Assemblies of glutamate receptor subunits with post-synaptic density proteins and their alterations in Parkinson's disease.