JNK Pathway as Therapeutic Target to Prevent Degeneration in the Central Nervous System
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JNKs (c-Jun N-terminal kinases) are important transducing enzymes involved in many faces of cellular regulation such as gene expression, cell proliferation and programmed cell death. The activation of JNK pathway is critical for naturally occurring neuronal death during development as well as for pathological death of adult brain following different insults. In particular, JNKs play an important role in excitotoxicity and all related phenomena. Initial research concentrated on defining the components and organization of JNK signalling cascades, but more recent studies have begun to see JNK as the appropriate target for prevent cell loss. We used a specific JNK inhibitor, the cell permeable peptide D-JNKI1, to block JNK action in neuronal death following excitotoxicity in vitro and cerebral ischemia in vivo. Here we review our recent findings and we discuss the possibility of using D-JNKI1 as a therapeutic agent to prevent cell loss in the central nervous system.
Key WordsJNK inhibitors excitotoxicity neurodegeneration ischemic damage
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- 11.Brecht S, Kirchhof R, Chromik A, Willesen M, Nicolaus T, Raivich G, Wessig J, Waetzig V, Goetz M, Claussen M, Pearse D, Kuan CY, Vaudano E, Behrens A, Wagner E, Flavell RA, Davis RJ, and Herdegen T. Specific pathophysiological functions of JNK isoforms in the brain. Eur J Neurosci 21: 363–377, 2005.PubMedCrossRefGoogle Scholar
- 14.Coffey ET, Smiciene G, Hongisto V, Cao J, Brecht S, Herdegen T, and Courtney MJ. c-Jun N-terminal protein kinase (JNK) 2/3 is specifically activated by stress, mediating c-Jun activation, in the presence of constitutive JNK1 activity in cerebellar neurons. J Neurosci 22: 4335–4345, 2002.PubMedGoogle Scholar
- 33.Standen CL, Brownlees J, Grierson AJ, Kesavapany S, Lau KF, McLoughlin DM, and Miller CC. Phosphorylation of thr(668) in the cytoplasmic domain of the Alzheimer’s disease amyloid precursor protein by stress-activated protein kinase 1b (Jun N-terminal kinase-3). J Neurochem 76: 316–320, 2001.PubMedCrossRefGoogle Scholar