title: Anti-apoptotic therapy with a Tat fusion protein protects against excitotoxic insults in vitro and in vivo.
abstract: A number of gene therapy approaches have been developed for protecting neurons from necrotic neurological insults. Such therapies are limited by the need for transcription and translation of the protective protein, delaying therapeutic impact. As an alternative, we explore the neuroprotective potential of protein therapy, using a fusion protein comprised of the death-suppressing BH4 domain of the Bcl-xL protein and the protein transduction domain of the human immunodeficiency virus Tat protein. This fusion protein decreased neurotoxicity caused by the excitotoxins glutamate and kainic acid in primary hippocampal cultures, and decreased hippocampal damage in vivo in an excitotoxic seizure model.
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Ju
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Manley
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sapolsky
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004347:Drug Interactions; D004622:Embryo, Mammalian; D015696:Gene Products, tat / Q000096:biosynthesis / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000627:therapeutic use*; D051020:bcl-X Protein / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D015696:Gene Products, tat; D011994:Recombinant Proteins; D051020:bcl-X Protein; D018698:Glutamic Acid; D007608:Kainic Acid