title: Lack of Jun-N-terminal kinase 3 (JNK3) does not protect against neurodegeneration induced by 3-nitropropionic acid.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Institut de Biomedicina, Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Universitat de Barcelona, Barcelona, Spain. felixjunyent@ub.edu
authors: F
authors: F
authors: Junyent
authors: L
authors: L
authors: de Lemos
authors: E
authors: E
authors: Verdaguer
authors: M
authors: M
authors: Pallàs
authors: J
authors: J
authors: Folch
authors: C
authors: C
authors: Beas-Zárate
authors: A
authors: A
authors: Camins
authors: C
authors: C
authors: Auladell
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003292:Convulsants / Q000633:toxicity; D003342:Corpus Striatum / Q000201:enzymology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006816:Huntington Disease / Q000201:enzymology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology*; D009574:Nitro Compounds / Q000633:toxicity; D011422:Propionates / Q000633:toxicity
chemical_list: D003292:Convulsants; D009574:Nitro Compounds; D011422:Propionates; D048057:Mitogen-Activated Protein Kinase 10; C015392:3-nitropropionic acid