| Peptide action in stroke therapy. | |
| | |
MedLine Citation:
|
PMID: 14519074 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Michelle M Aarts; Michael Tymianski |
Related Documents
:
|
11948244 - Effects of estrogen treatment on glutamate uptake in cultured human astrocytes derived ... 14657164 - Cannabinoids decrease corticostriatal synaptic transmission via an effect on glutamate ... 11885654 - Neurotransmission of the cochlear inner hair cell synapse--implications for inner ear t... 7715804 - Involvement of the glutamate receptor delta 2 subunit in the long-term depression of gl... 8150214 - Receptor subtype and intracellular signal transduction pathway associated with situs in... 16682964 - Mu opioid and cb1 cannabinoid receptor interactions: reciprocal inhibition of receptor ... |
Publication Detail:
|
Type: Journal Article; Review |
Journal Detail:
|
Title: Expert opinion on biological therapy Volume: 3 ISSN: 1471-2598 ISO Abbreviation: Expert Opin Biol Ther Publication Date: 2003 Oct |
Date Detail:
|
Created Date: 2003-10-01 Completed Date: 2004-07-19 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 101125414 Medline TA: Expert Opin Biol Ther Country: England |
Other Details:
|
Languages: eng Pagination: 1093-104 Citation Subset: IM |
Affiliation:
|
Toronto Western Hospital, Suite 4W-435, 399 Bathurst Street, Toronto, Ontario, M5T 2S8, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Humans Peptides / therapeutic use* Receptors, Glutamate / drug effects Signal Transduction / drug effects Stroke / physiopathology, therapy* |
| Chemical | |
Reg. No./Substance:
|
0/Peptides; 0/Receptors, Glutamate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Polyethyleneimine-based gene therapy by inhalation.
Next Document: The role of fibrinogen and related fragments in tumour angiogenesis and metastasis.