Regulation of GSK-3β by calpain in the 3-nitropropionic acid model

N. Crespo-Biel, A. Camins, J. Gutiérrez-Cuesta, D. Melchiorri, F. Nicoletti, M. Pallàs, Anna Maria Canudas

Research output: Contribution to journalArticlepeer-review


Glycogen synthase kinase-3β (GSK-3β) is a crucial component in the cascade of events that culminate in a range of neurodegenerative diseases. It is controlled by several pathways, including calpain-mediated cleavage. Calpain mediates in cell death induced by 3-nitropropionic acid (3-NP), but GSK-3β regulation has not been demonstrated. Here we studied changes in total GSK-3β protein levels and GSK-3β phosphorylation at Ser-9 in this model. The 3-NP treatment induced GSK-3β truncation. This regulation was dependent on calpain activation, since addition of calpeptin to the medium prevented this cleavage. While calpain inhibition prevented 3-NP-induced neuronal loss, inhibition of GSK-3β by SB-415286 did not. Furthermore, inhibition of cdk5, a known target of calpain involved in 3-NP-induced cell death, also failed to rescue neurons in our model. Our results point to a new target of calpain and indicate possible cross-talk between calpain and GSK-3β in the 3-NP toxicity pathway. On the basis of our findings, we propose that calpain may modulate 3-NP-induced neuronal loss.

Original languageEnglish
Pages (from-to)962-970
Number of pages9
Issue number8
Publication statusPublished - Aug 2010


  • Calpeptin
  • Caspase
  • Cdk5
  • SB-415286
  • Spectrin

ASJC Scopus subject areas

  • Cognitive Neuroscience


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