4.5 Article

Blockade of the translocation and activation of c-Jun N-terminal kinase 3 (JNK3) attenuates dopaminergic neuronal damage in mouse model of Parkinson's disease

Journal

NEUROCHEMISTRY INTERNATIONAL
Volume 54, Issue 7, Pages 418-425

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2009.01.013

Keywords

JNK3; Activation; Translocation; N-Acetylcysteine; Ketamine; Parkinson's disease

Funding

  1. National Program of Basic Research [2006CB500706]
  2. National Natural Science [30471918, 30570637]
  3. Shanghai Key Project of Basic Science Research [04DZ14005]
  4. Program for Outstanding Medical Academic [LJ 06003]

Ask authors/readers for more resources

Increasing evidence suggests that c-Jun N-terminal kinase (JNK) is an important kinase mediating neuronal death in Parkinson's disease (PD) model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). JNK3, the only neural-specific isoform, may play an important role in mediating the neurotoxic effects of MPTP in dopaminergic neuronal injury. To analyze the variation in JNK3 activation, the levels of phospho-JNK3 were measured at the various time points of occurrence of MPTP-induced lesions. In our study, we observed that during MPTP intoxication, two peaks of JNK3 activation appeared at 8 and 24 h. To further define the mechanism of JNK3 activation and translocation, the antioxidant N-acetylcysteine (NAC), the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, and the alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist 6,7dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) were administered to the mice 30 min after each of the four MPTP injections. The results revealed that NAC clearly inhibited JNK3 activation during the early intoxication, whereas ketamine preferably attenuated JNK3 activation during the latter intoxication. DNQX had no significant effects on JNK3 activation during intoxication. Consequently, reactive oxygen species (ROS) and the NMDA receptor were closely associated with JNK3 activation following MPTP intoxication. NAC and ketannine exerted a preventive effect against MPTP-induced loss of tyrosine hydroxylase-positive neurons and suppressed the nuclear translocation of JNK3, suggesting that NAC and ketamine can prevent MPTP-induced dopaminergic neuronal death by suppressing JNK3 activation. (C) 2009 Elsevier Ltd. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available