兴奋毒性
谷氨酸受体
谷氨酸的
神经传递
神经科学
受体
生物
兴奋性突触后电位
突触后电位
药理学
细胞生物学
抑制性突触后电位
生物化学
作者
Michelle Aarts,Michael Tymianski
标识
DOI:10.1517/14712598.3.7.1093
摘要
Glutamate receptor antagonists, although effective in preventing in vitro excitotoxic death, also block the glutamatergic signalling that is essential for normal excitatory neurotransmission and neuronal survival. This has contributed to the failure of clinical trials employing glutamate receptor antagonists as stroke therapeutics. However, recent years have seen an increased understanding of the molecular organisation of glutamate receptors in the neuronal postsynaptic density. This and a dissection of their associated intracellular signalling cascades has allowed the identification of distinct pathways responsible for excitotoxicity. It has become possible to uncouple toxic signalling cascades from glutamate receptors by targeting the interactions of membrane receptors with downstream proteins. Toxic signalling can be effectively uncoupled from glutamate receptors using targeted, cell-permeable peptides to disrupt specific protein-protein interactions. This approach does not block essential excitatory neurotransmission, but attenuates neurotoxic signals specifically and reduces stroke damage. This novel approach to blocking excitotoxic signalling in cerebral ischaemia may constitute a practical approach to stroke therapy.
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