FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neuron diseases
| Autor: | Mojsilovic-Petrovic, J., Nedelsky, N., Boccitto, M., Mano, I., Georgiades, Savvas N., Zhou, W., Liu, Y., Neve, R. L., Taylor, J. P., Driscoll, M., Clardy, J., Merry, D., Kalb, R. G. |
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| Přispěvatelé: | Georgiades, Savvas N. [0000-0002-6106-9904] |
| Rok vydání: | 2009 |
| Předmět: |
Cell Culture Techniques
nerve degeneration Cell Count Rats Sprague-Dawley Mice androgen receptor Excitatory Amino Acid Agonists rat Motor Neurons Kainic Acid Cell Death General Neuroscience Neurodegeneration Forkhead Box Protein O3 article transcription factor DAF 16 Forkhead Transcription Factors Immunohistochemistry medicine.anatomical_structure Neuroprotective Agents priority journal Spinal Cord motor neuron disease transcription factor FKHRL1 Female Drosophila neuroprotection Signal transduction Neuron death excitotoxicity signal transduction Signal Transduction Programmed cell death in vitro study animal experiment Blotting Western embryo Biology Neuroprotection Article Fluorescence animal tissue in vivo study male In vivo medicine Animals controlled study Motor Neuron Disease protein expression mouse nonhuman nerve cell necrosis animal model Computational Biology Motor neuron medicine.disease Embryo Mammalian nuclear localization signal Rats Androgen receptor Mice Inbred C57BL Disease Models Animal Tyrosine Neuroscience |
| Zdroj: | Journal of Neuroscience J.Neurosci. |
| Popis: | Aging is a risk factor for the development of adult-onset neurodegenerative diseases. Although some of the molecular pathways regulating longevity and stress resistance in lower organisms are defined (i.e., those activating the transcriptional regulators DAF-16 and HSF-1 in Caenorhabditis elegans), their relevance to mammals and disease susceptibility are unknown. We studied the signaling controlled by the mammalian homolog of DAF-16, FOXO3a, in model systems of motor neuron disease. Neuron death elicited in vitro by excitotoxic insult or the expression of mutant SOD1, mutant p150glued, or polyQ-expanded androgen receptor was abrogated by expression of nuclear-targeted FOXO3a. We identify a compound [Psammaplysene A (PA)] that increases nuclear localization of FOXO3a in vitro and in vivo and show that PA also protects against these insults in vitro. Administration of PA to invertebrate model systems of neurodegeneration similarly blocked neuron death in a DAF-16/FOXO3a-dependent manner. These results indicate that activation of the DAF-16/FOXO3a pathway, genetically or pharmacologically, confers protection against the known causes of motor neuron diseases. Copyright © 2009 Society for Neuroscience. 29 25 8236 8247 Cited By :52 |
| Databáze: | OpenAIRE |
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