Unconjugated TAT carrier peptide protects against excitotoxicity.
We report in this article for the first time the neuroprotective effects of unconjugated TAT carrier peptide against a mild excitotoxic stimulus both in vitro and in vivo. In view of the widespread use of TAT peptides to deliver neuroprotectants into cells, it is important to know the effects of the carrier itself. Unconjugated TAT carrier protects dissociated cortical neurons against NMDA but not against kainate, suggesting that TAT peptides may interfere with NMDA signaling. Furthermore, a retro-inverso form of the carrier peptide caused a reduction in lesion volume (by about 50%) in a rat neonatal cerebral ischemia model. Thus, even though TAT is designed merely as a carrier, its own pharmacological activity will need to be considered in the analysis of TAT-linked neuroprotectant peptides.
Vaslin
Anne
A
Département de Biologie Cellulaire et de Morphologie, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland. anne.vaslin@hotmail.com
Rummel
Coralie
C
Clarke
Peter G H
PG
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D054322:tat Gene Products, Human Immunodeficiency Virus; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; D007608:Kainic Acid