期刊
NEUROPHARMACOLOGY
卷 56, 期 2, 页码 422-428出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2008.09.012
关键词
Lithium; 3-Nitropropionic acid; Calpain; Neurodegenerative disease; Spectrin; Calcium; p35
资金
- Ministerio de Educacion y Ciencia (Spain) [SAF-2006-13092]
- Centros de lnvestigacion Biomedica en Red (CIBER) from the Instituto de Salud Carlos 111 [P1041300]
- Generalitat de Catalunya [2005/SGR00893]
- la Obra Social Caixa de Sabadell and la Fundacio La Marato [063203]
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. (c) 2008 Elsevier Ltd. All rights reserved.
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