Evidence of calpain/cdk5 pathway inhibition by lithium in 3-nitropropionic acid toxicity in vivo and in vitro

Crespo-Biel, N.; Camins, A.; Pallas, M.; Canudas, A. M.


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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Título según WOS: ID WOS:000263454200011 Not found in local WOS DB
Título de la Revista: NEUROPHARMACOLOGY
Volumen: 56
Número: 2
Fecha de publicación: 2009
Página de inicio: 422
Página final: 428


Notas: ISI