title: Small peptide inhibitor of JNK3 protects dopaminergic neurons from MPTP induced injury via inhibiting the ASK1-JNK3 signaling pathway.
abstract: OBJECTIVE
  The ASK1-JNK3 signaling pathway plays a pivotal role in the pathogenesis of Parkinson's disease (PD). The specific binding of β-arrestin2 to JNK3 is essential for activation of the ASK1-JNK3 cascade, representing a potential therapeutic target for preventing dopaminergic neuronal death in PD. The aim of this study was to identify a novel strategy for the prevention of dopaminergic neuronal death in PD.
  
  
  METHODS
  Based on the specific binding of β-arrestin2 to JNK3, a 21-amino-acid fusion peptide, termed JNK3-N-Tat, was synthesized. We evaluated the ability of this peptide to inhibit the binding of β-arrestin2 to its target domain in JNK3 in vitro and in vivo.
  
  
  RESULTS
  The JNK3-N-Tat peptide inhibited activation of the ASK1-JNK3 cascade by disrupting the interaction between β-arrestin2 and JNK3. JNK3-N-Tat exerted beneficial effects through pathways downstream of JNK3 and improved mitochondrial function, resulting in attenuated MPP+/MPTP-induced damage. JNK3-N-Tat protected mesencephalic dopaminergic neurons against MPTP-induced toxicity.
  
  
  CONCLUSIONS
  JNK3-N-Tat, a JNK3-inhibitory peptide, protects dopaminergic neurons against MPP+/MPTP-induced injury by inhibiting the ASK1-JNK3 signaling pathway.
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Jing
authors: J
authors: Pan
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Hui
authors: H
authors: Li
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Bei
authors: B
authors: Zhang
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Ran
authors: R
authors: Xiong
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Wen-Yan
authors: WY
authors: Kang
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Wei
authors: W
authors: Chen
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zong-Bo
authors: ZB
authors: Zhao
authors: Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Stem Cell Biology & Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Science (CAS) and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Sheng-Di
authors: SD
authors: Chen
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019390:Arrestins / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D048057:Mitogen-Activated Protein Kinase 10 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D000071557:beta-Arrestins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D048057:Mitogen-Activated Protein Kinase 10; D048848:MAP Kinase Kinase Kinase 5