2. Academic Validation
  3. Design and Synthesis of a Mitochondrial-Targeted JNK Inhibitor and Its Protective Effect on Parkinson's Disease Phenotypes

Design and Synthesis of a Mitochondrial-Targeted JNK Inhibitor and Its Protective Effect on Parkinson's Disease Phenotypes

  • Chembiochem. 2023 Jul 3;24(13):e202200748. doi: 10.1002/cbic.202200748.
Zhiqiang Zhou 1,  Duoteng Zhang 2,  Fangning Du 1,  Weizhen An 1,  Jingyan Ge 3,  Changmin Yu 1,  Naidi Yang 1,  Chengwu Zhang 4,  Kahleong Lim 5,  Lin Li 1 2
Affiliations

Affiliations

  • 1 Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University, 5 Xinmofan Road, Nanjing, 211816, P. R. China.
  • 2 The Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, 422 Siming South Road, Xiamen, 361005, P. R. China.
  • 3 Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310014, P. R. China.
  • 4 School of Basic Medical Sciences, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 310003, P. R. China.
  • 5 Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 302238, Singapore, Singapore.
PMID: 36946263 DOI: 10.1002/cbic.202200748
Abstract

C-Jun N-terminal kinase (JNK) is a key mediator involved in a variety of physiological processes. JNK activation is regulated in a complex manner by upstream kinases and phosphatases, and plays an important role in physiological processes such as the immune response and neuronal function. Therefore, JNK has become a therapeutic target for neurodegenerative diseases, ankylosing spondylitis, psoriasis, arthritis and Other Diseases. Inhibition of JNK activation in mitochondria holds great potential for Parkinson's disease (PD) therapy. However, no specific mitochondrial-targeted JNK Inhibitor has been reported. We have developed a mitochondrial-targeted JNK Inhibitor, P2, by linking a mitochondrial-specific cell-penetrating peptide to SP600125 (SP), a commercialized specific inhibitor of JNK. We found that P2 specifically inhibited mitochondrial JNK phosphorylation instead of nuclear JNK signaling. Further studies showed that P2 effectively rescued PD phenotypes both in vitro and in vivo, thus indicating that it is a potential therapeutic for PD.

Keywords

C-Jun N-terminal kinase; Parkinson's disease; inhibitors; mitochondria; mitochondrial targeting.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-155077
    JNK抑制剂
    JNK
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