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The Cerebellum

Erschienen in:

01.12.2008

Specific JNK Inhibition by D-JNKI1 Protects Purkinje Cells from Cell Death in Lurcher Mutant Mouse

verfasst von: Mariaelena Repici, Hadi S. Zanjani, Vanessa Gautheron, Tiziana Borsello, Isabelle Dusart, Jean Mariani

Erschienen in: The Cerebellum | Ausgabe 4/2008

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Abstract

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.

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Titel: Specific JNK Inhibition by D-JNKI1 Protects Purkinje Cells from Cell Death in Lurcher Mutant Mouse
verfasst von: Mariaelena Repici
Hadi S. Zanjani
Vanessa Gautheron
Tiziana Borsello
Isabelle Dusart
Jean Mariani
Publikationsdatum: 01.12.2008
Verlag: Springer-Verlag
Erschienen in: The Cerebellum / Ausgabe 4/2008
Print ISSN: 1473-4222
Elektronische ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-008-0070-8

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