Publication Date:
2002-10-26
Description:
N-methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein PSD-95. This procedure dissociated NMDARs from downstream neurotoxic signaling without blocking synaptic activity or calcium influx. The peptides, when applied either before or 1 hour after an insult, protected cultured neurons from excitotoxicity, reduced focal ischemic brain damage in rats, and improved their neurological function. This approach circumvents the negative consequences associated with blocking NMDARs and may constitute a practical stroke therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aarts, Michelle -- Liu, Yitao -- Liu, Lidong -- Besshoh, Shintaro -- Arundine, Mark -- Gurd, James W -- Wang, Yu-Tian -- Salter, Michael W -- Tymianski, Michael -- NS 39060/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):846-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Toronto Western Hospital Research Institute, 11-416 MC-PAV, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12399596" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Brain/*drug effects/metabolism
;
Brain Ischemia/*drug therapy/metabolism
;
Calcium/metabolism
;
Cells, Cultured
;
Cerebral Infarction/*drug therapy/metabolism
;
Cyclic GMP/metabolism
;
Guanylate Kinase
;
In Vitro Techniques
;
Intracellular Signaling Peptides and Proteins
;
Male
;
Membrane Proteins
;
Mice
;
Mice, Inbred C57BL
;
N-Methylaspartate/pharmacology
;
Nerve Tissue Proteins/chemistry/*metabolism
;
Neurons/drug effects/physiology
;
Patch-Clamp Techniques
;
Peptides/administration & dosage/*pharmacology/therapeutic use
;
Protein Binding
;
Rats
;
Rats, Sprague-Dawley
;
Rats, Wistar
;
Receptors, N-Methyl-D-Aspartate/*chemistry/*metabolism
;
Recombinant Fusion Proteins/administration & dosage/pharmacology/therapeutic use
;
Signal Transduction
;
Synaptic Transmission/drug effects
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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