Article
Multidisciplinary Sciences
Jiao Luo, Xiujun Tan, Ling Ye, Chenglin Wang
Summary: The study reveals that the JNK signaling pathway plays a positive role in the formation of dental papilla cell polarity, as indicated by the up-regulation of polarity-related genes and rescue effects of RhoA Q63L mutant. JNK activation is linked to polarization, migration, and differentiation of dental papilla cells, highlighting its importance in tooth development.
Article
Medicine, Research & Experimental
Rika Kurogoushi, Tomokazu Hasegawa, Yuki Akazawa, Kokoro Iwata, Asuna Sugimoto, Kimiko Yamaguchi-Ueda, Aya Miyazaki, Anrizandy Narwidina, Keita Kawarabayashi, Takamasa Kitamura, Hiroshi Nakagawa, Tomonori Iwasaki, Tsutomu Iwamoto
Summary: This study revealed that FGF2 regulates the expression of CCL11 in human dental pulp-derived MSCs through the JNK signaling pathway, providing important insights for dental tissue regeneration therapy.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Jing Tan, Wei Gao, Wanchao Yang, Xianzhang Zeng, Linlin Wang, Xiaoguang Cui
Summary: JNK1 exacerbates ischemia-reperfusion injury in lung transplantation, while JNK2 alleviates it. JNK1 silencing attenuates lung graft dysfunction by inhibiting inflammation and apoptosis.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Biochemistry & Molecular Biology
Masashi Okada, Yurika Nakagawa-Saito, Yuta Mitobe, Asuka Sugai, Keita Togashi, Shuhei Suzuki, Chifumi Kitanaka
Summary: Glioma stem cells (GSCs) play a critical role in the malignancy of glioblastoma multiforme (GBM) by resisting therapy and promoting tumor initiation. This study reveals that phospholipase C (PLC) epsilon is highly expressed in GSCs and maintains their stemness and survival capacity through the activation of JNK pathway. PLC epsilon may serve as a promising therapeutic target for GSCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Keiko Tanimura, Tadaaki Yamada, Mano Horinaka, Yuki Katayama, Sarina Fukui, Kenji Morimoto, Takayuki Nakano, Shinsaku Tokuda, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko Kaneko, Junji Uchino, Kazue Yoneda, Seiji Yano, Toshiyuki Sakai, Koichi Takayama
Summary: Through activation of the JNK/c-Jun signaling, novel adaptive resistance has been identified as a key factor leading to failure of ALK-TKIs treatment, suggesting that combination therapy targeting JNK and ALK-TKIs may significantly delay regrowth of lung cancer cells and potentially improve patient outcomes.
Review
Biochemistry & Molecular Biology
Hyunwook Cho, Jung-Mi Hah
Summary: JNK3 plays a crucial role in neurodegenerative diseases, and this study summarizes the research on JNK3 inhibitors, focusing on structural and docking insights.
Article
Gastroenterology & Hepatology
Zhigang Fang, Hyeong-Geug Kim, Menghao Huang, Kushan Chowdhury, Ming O. Li, Suthat Liangpunsakul, X. Charlie Dong
Summary: This study demonstrates the protective role of Sesn1/2/3 in hepatic lipotoxicity-induced oxidative stress by reducing JNK phosphorylation and activity, leading to decreased lipotoxicity and oxidative stress in liver cells.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anna A. Zhdankina, Dmitry I. Tikhonov, Sergey V. Logvinov, Mark B. Plotnikov, Andrei I. Khlebnikov, Nataliya G. Kolosova
Summary: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. JNK inhibitor IQ-1S shows potential in preventing and treating AMD, as it improves histological abnormalities associated with retinopathy in the OXYS rat model, including improved blood circulation, increased functional activity of the retinal pigment epithelium, reduced VEGF expression, and increased PEDF expression.
Article
Biochemistry & Molecular Biology
Igor A. Schepetkin, Oleksander S. Karpenko, Anastasia R. Kovrizhina, Liliya N. Kirpotina, Andrei I. Khlebnikov, Stepan I. Chekal, Alevtyna V. Radudik, Maryna O. Shybinska, Mark T. Quinn
Summary: The JNK family, including JNK1-3 proteins, regulates various physiological processes. The study aimed to find JNK inhibitors with high selectivity for JNK3. 26 new tryptanthrin-6-oxime analogs were synthesized and evaluated, and compounds 4d and 4e showed high selectivity for JNK3 and inhibited inflammatory responses. The results suggest the potential for developing anti-inflammatory drugs with selectivity for JNK3.
Article
Agriculture, Multidisciplinary
Wan Wang, Cong Xu, Xuan Zhou, Le Zhang, Liya Gu, Zhijing Liu, Jiage Ma, Juncai Hou, Zhanmei Jiang
Summary: This study explored the effects of probiotics and prebiotics in alleviating neurodegenerative diseases. The combination of Lactobacillus plantarum and galactooligosaccharides was found to reduce oxidative stress and increase levels of nuclear factor erythroid 2-related factor 2 in the brain. Additionally, the combination regulated the gut microbiota metabolite butyrate, which inhibited expression of p-JNK, downregulated pro-apoptotic proteins and inflammatory mediators, and upregulated synaptic protein expression. This suggests that Lactobacillus plantarum combined with galactooligosaccharides may have potential in alleviating neurodegeneration and memory impairment induced by D-galactose.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lina Lorenzen, Dennis Frank, Carsten Schwan, Robert Grosse
Summary: FMNL2 is upregulated in several cancers and plays important roles in cell migration, invasion, cell-cell adhesion and filopodia formation. Using structured illumination microscopy, it was found that FMNL2 promotes rapid and highly dynamic filopodia formation in epithelial cells while remaining on the tip of the growing filopodia. This filopodia tip localization depends on its N-terminal myristoylation and serine 1072 phosphorylation within the diaphanous-autoregulatory domain (DAD) by protein kinase C (PKC) alpha.
Article
Chemistry, Medicinal
Hewen Qian, Yuanqing Ding, Xingyu Deng, Weiwei Huang, Zhenzhen Li, Fengling Liu, Jie Zhang, Lihui Wang, Junping Liu, Yaxia Yuan, Shurong Hou, Xiabin Chen, Lei Ma
Summary: In this study, a strategy based on computational prediction of synthetic feasibility and fragment-based molecule generation was used to design JNK1 inhibitors. Several potent JNK1 inhibitors were discovered, with compound C6 exhibiting comparable activity to the clinical candidate CC-90001. Compound C6 could be synthesized in only two steps, compared to nine steps for CC-90001. These findings suggest that compound C6 is a promising lead for further optimization and development as a novel anti-fibrotic agent targeting JNK1.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shi-Bei Wu, Tzu-Yu Hou, Hui-Chuan Kau, Chieh-Chih Tsai
Summary: The study found that pirfenidone modulates TGF-beta 1-mediated myofibroblast differentiation and ECM homeostasis by attenuating downstream signaling of TGF-beta 1. It reduces the expression of fibrotic proteins and recovers metalloproteinase activities, showing its potential in inhibiting fibrosis in orbital fibroblasts.
Article
Biochemistry & Molecular Biology
Masanori Itakura, Takeya Kubo, Akihiro Kaneshige, Hidemitsu Nakajima
Summary: GAPDH interacts with JNK and promotes its activation under oxidative stress, which is dependent on the oxidation of the active-site cysteine (Cys152) in GAPDH. Inhibition of GAPDH expression reduces JNK activation and attenuates the translocation of Bax protein to mitochondria. Therefore, GAPDH plays a significant role in the JNK signaling pathway under oxidative stress.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Serhii A. Liakhov, Igor A. Schepetkin, Olexander S. Karpenko, Hanna Duma, Nadiia M. Haidarzhy, Liliya N. Kirpotina, Anastasia R. Kovrizhina, Andrei Khlebnikov, Irina Y. Bagryanskaya, Mark T. Quinn
Summary: In this study, 13 derivatives of a JNK inhibitor were synthesized, with 8 compounds showing submicromolar binding affinity for at least one JNK isoform, and most of them exhibiting anti-inflammatory effects. Selected compounds also directly confirmed JNK inhibition, indicating their potential as lead compounds for anti-inflammatory drug development.
