Abstract
The central nervous system has the capacity to activate profound neuroprotection following sub-lethal stress in a process termed preconditioning. To gain insight into this potent survival response we developed a functional cloning strategy that identified 31 putative neuroprotective genes of which 28 were confirmed to provide protection against oxygen-glucose deprivation (OGD) or excitotoxic exposure to N-methyl-D-aspartate (NMDA) in primary rat cortical neurons. These results reveal that the brain possesses a wide and diverse repertoire of neuroprotective genes. Further characterization of these and other protective signals could provide new treatment opportunities for neurological injury from ischemia or neurodegenerative disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-Ribosylation Factors / genetics
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ADP-Ribosylation Factors / metabolism
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Animals
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Blotting, Northern
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Calmodulin / genetics
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Calmodulin / metabolism
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Cell Survival / drug effects
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Cell Survival / genetics
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Cells, Cultured
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Excitatory Amino Acid Agonists / pharmacology
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Fibroblasts / cytology
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Fibroblasts / metabolism*
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Gene Expression / drug effects
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Glucose / pharmacology
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HEK293 Cells
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Humans
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Immunoblotting
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Mice
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Mice, Knockout
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N-Methylaspartate / pharmacology
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Neurons / cytology
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Neurons / metabolism*
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Oxygen / pharmacology
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Poly(ADP-ribose) Polymerases / genetics
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Poly(ADP-ribose) Polymerases / metabolism
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Proteins / genetics*
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Proteins / metabolism
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RNA Interference
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Rats
Substances
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Calmodulin
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Excitatory Amino Acid Agonists
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Proteins
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N-Methylaspartate
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Poly(ADP-ribose) Polymerases
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ADP-Ribosylation Factors
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Arl4D protein, mouse
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Glucose
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Oxygen