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The excitatory neurotransmitter glutamate stimulates DNA repair to increase neuronal resiliency
- Source :
- Mechanisms of Ageing and Development. 132:405-411
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Glutamate is the most abundant excitatory neurotransmitter in the vertebrate central nervous system and plays an important role in synaptic plasticity required for learning and memory. Activation of glutamate ionotropic receptors promptly triggers membrane depolarization and Ca 2+ influx, resulting in the activation of several different protein kinases and transcription factors. For example, glutamate-mediated Ca 2+ influx activates Ca 2+ /calmodulin-dependent kinase, protein kinase C, and mitogen activated protein kinases resulting in activation of transcription factors such as cyclic AMP response element binding protein (CREB). Abnormally prolonged exposure to glutamate causes neuronal injury, and such “excitotoxicity” has been implicated in many acute and chronic diseases including ischemic stroke, epilepsy, amyotrophic lateral sclerosis, Alzheimer's, Huntington's and Parkinson's diseases. Interestingly, although glutamate-induced Ca 2+ influx can cause DNA damage by a mitochondrial reactive oxygen species-mediated mechanism, the Ca 2+ simultaneously activates CREB, resulting in up-regulation of the DNA repair and redox protein apurinic/apyrimidinic endonuclease 1. Here, we review connections between physiological or aberrant glutamate receptor activation, Ca 2+ -mediated signaling, oxidative DNA damage and repair efficiency, and neuronal vulnerability. We conclude that glutamate signaling involves an adaptive cellular stress response pathway that enhances DNA repair capability, thereby protecting neurons against injury and disease.
- Subjects :
- Aging
DNA Repair
Excitotoxicity
Glutamic Acid
Biology
medicine.disease_cause
CREB
Article
medicine
Animals
Humans
Calcium Signaling
Cyclic AMP Response Element-Binding Protein
Protein Kinase C
Neurons
Neurotransmitter Agents
Metabotropic glutamate receptor 6
Glutamate receptor
Neurodegenerative Diseases
Glutamic acid
Molecular biology
Mitochondria
Cell biology
Metabotropic glutamate receptor
biology.protein
Metabotropic glutamate receptor 1
NMDA receptor
Calcium
Reactive Oxygen Species
Oxidation-Reduction
Developmental Biology
Subjects
Details
- ISSN :
- 00476374
- Volume :
- 132
- Database :
- OpenAIRE
- Journal :
- Mechanisms of Ageing and Development
- Accession number :
- edsair.doi.dedup.....bec839dc3445825505ab70c9decb3b0c