Specific JNK inhibition by D-JNKI1 protects Purkinje cells from cell death in Lurcher mutant mouse

Mariaelena Repici, Hadi S Zanjani, Vanessa Gautheron, Tiziana Borsello, Isabelle Dusart, Jean Mariani

Research output: Contribution to journalArticlepeer-review


In the Lurcher mutant mouse (+/Lc), Purkinje cells (PCs) selectively die due to the mutation that converts alanine to threonine in the glutamate ionotropic receptor GRID 2, thus resulting in a constitutively leaky cation channel. This intrinsic cell death determines a target-dependent cell death of granule cells and olivary neurons and cerebellum cytoarchitecture is severely disrupted in the adult Lurcher mutant. Although the +/Lc mutant has been widely characterized, less is known about the molecules involved in +/Lc PC death. We, here, used organotypic cerebellar slice cultures from P0 mice to investigate the role of c-jun N-terminal kinase (JNK) in +/Lc PC death by using D-JNKI1 as very specific tool to inhibit its action. Our results showed that D-JNKI1 treatment increased the number of +/Lc PC at 14 DIV of 3.6-fold. Conversely, this specific JNK inhibitor cell permeable peptide did not increase PC number in +/+ treated versus untreated cultures. These results clearly indicate that JNK plays an important role in +/Lc PC mechanism of cell death.

Original languageEnglish
Pages (from-to)534-538
Number of pages5
JournalThe Cerebellum
Issue number4
Publication statusPublished - 2008


  • Alanine/genetics
  • Amino Acid Substitution
  • Animals
  • Animals, Newborn
  • Cell Death
  • Cell Membrane Permeability
  • Cerebellum/cytology
  • Crosses, Genetic
  • Female
  • Genotype
  • MAP Kinase Kinase 4/antagonists & inhibitors
  • Male
  • Mice
  • Mice, Neurologic Mutants/physiology
  • Mutation
  • Neurons/enzymology
  • Peptides/physiology
  • Purkinje Cells/cytology
  • Receptors, Glutamate/genetics
  • Threonine/genetics


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