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Lack of Jun‐N‐terminal kinase 3 (JNK3) does not protect against neurodegeneration induced by 3‐nitropropionic acid
Author(s) -
Junyent F.,
de Lemos L.,
Verdaguer E.,
Pallàs M.,
Folch J.,
BeasZárate C.,
Camins A.,
Auladell C.
Publication year - 2012
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2011.01214.x
Subject(s) - neurodegeneration , neuroprotection , astrogliosis , programmed cell death , biology , kinase , apoptosis , microbiology and biotechnology , neuroscience , medicine , biochemistry , disease , central nervous system
F. Junyent, L. de Lemos, E. Verdaguer, M. Pallàs, J. Folch, C. Beas‐Zárate, A. Camins and C. Auladell (2012) Neuropathology and Applied Neurobiology 38, 311–321 Lack of Jun‐N‐terminal kinase 3 (JNK3) does not protect against neurodegeneration induced by 3‐nitropropionic acid Aims: 3‐Nitropropionic acid (3‐NP) is a toxin that replicates most of the clinical and pathophysiological symptoms of Huntington's disease, inducing neurodegeneration in the striatum due to the inhibition of mitochondrial succinate dehydrogenase. Different pathways have been implicated in the cell death induced by 3‐NP in rodents. One of them is the Jun‐N‐terminal kinase (JNK) pathway, which may play a role in the neurodegenerative process in different diseases. Moreover, the lack of one isoform of JNK (JNK3) has been associated with neuroprotection in different experimental models of neurodegeneration. Therefore, in the present study the role of JNK3 in the experimental Huntington's model induced by 3‐NP administration was evaluated. Methods: 3‐NP was intraperitoneally administered once a day for 3 days to wild‐type and Jnk3 ‐null mice. Coronal brain sections were used to determine cell death and astrogliosis in striatum. Western blots were performed to determine the involvement of different pathways in both wild‐type and Jnk3 ‐null mice. Results: Although JNK activation was observed following 3‐NP administration, the results indicate that the lack of JNK3 does not confer neuroprotection against 3‐NP toxicity. Thus, other pathways must be involved in the neurodegeneration induced in this model. One of the possible pathways towards 3‐NP‐induced apoptosis could involve the calpains, as their activity was increased in wild‐type and Jnk3 ‐null mice. Conclusion: Although JNK3 is a key protein involved in cell death in different neurodegenerative diseases, the present study demonstrates that the lack of JNK3 does not confer neuroprotection against 3‐NP‐induced neuronal death.