Abstract
Lithium reduced striatal neurodegeneration induced in rats by 3-nitropropionic acid inhibiting calpain activation. Lithium prevented an increase in cdk5 activity, as shown by the levels of the co-activator p35. Myocite enhancer factor 2 (MEF2), a downstream substrate for cdk5 with pro-survival activity, showed increased phosphorylation. In primary cultures of neurons treated with 3-NP, lithium also reduced protease activity mediated by calpain, cdk5 activation and cellular death. These observations indicate that lithium has a neuroprotective effect. Lithium treatment also reduced the intracellular increase in calcium induced by 3-NP. The finding that lithium mediates the modulation of the calpain/cdk5 pathway further supports its use in the treatment of neurodegenerative diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Calpain / metabolism*
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Cell Survival / drug effects
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Cells, Cultured
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Cyclin-Dependent Kinase 5 / metabolism*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Interactions
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Embryo, Mammalian
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Gene Expression Regulation / drug effects
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Hippocampus / cytology
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Huntington Disease* / chemically induced
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Huntington Disease* / drug therapy
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Huntington Disease* / metabolism
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Lithium Chloride / therapeutic use*
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Male
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Mice
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Neurons / drug effects
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Neuroprotective Agents / therapeutic use*
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Nitro Compounds*
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Propionates*
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / drug effects*
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Succinate Dehydrogenase / metabolism
Substances
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Neuroprotective Agents
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Nitro Compounds
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Propionates
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Succinate Dehydrogenase
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Cyclin-Dependent Kinase 5
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Calpain
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Lithium Chloride
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3-nitropropionic acid
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Calcium