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
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
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
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.
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
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)
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
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
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
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
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
Pharmacology & Pharmacy
Yan Hu, Zhe Zhao, Yuan-Ting Liu, Ze-Cheng Xu, Jing-Yi Li, Zheng-Yu Yang, Yun-Qi Yang, Jia-Hui Zhang, Si-Yuan Qiu, Tao He, Yi-Ying Wu, Sha Liu
Summary: This study found that NITyr inhibits non-small cell lung cancer (NSCLC) by activating CB1 and CB2 receptors, involving the PI3K and ERK pathways. It inhibits cell proliferation, blocks the cell cycle, induces apoptosis, and inhibits migration.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Khairy A. Ibrahim, Hala A. Abdelgaid, Mohammed Eleyan, Rania A. Mohamed, Noha M. Gamil
Summary: The study found that resveratrol (RSV) can improve FNT-induced cardiac apoptosis. RSV alleviates cardiac oxidative damage and inflammation caused by FNT by modulating the SIRT1/c-JNK/p53 pathway and cellular redox status. RSV also improves histopathological changes in the heart.
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
Multidisciplinary Sciences
Jake W. Willows, Gilian Gunsch, Emma Paradie, Magdalena Blaszkiewicz, Jeffrey R. Tonniges, Maria F. Pino, Steven R. Smith, Lauren M. Sparks, Kristy L. Townsend
Summary: Peripheral neuropathy, including axonal degeneration and demyelination, affects adipose tissues in obesity, diabetes, and aging. This study investigated the presence of demyelinating neuropathy in adipose tissue and found that adipose tissue contains myelinated and unmyelinated nerves populated by Schwann cells (SCs), which play a role in nerve regeneration. The study also showed that SCs in adipose tissue become dysregulated in diabetic peripheral neuropathy.
Article
Cell Biology
Elizabeth K. Unger, Kenneth J. Burke, Cindy F. Yang, Kevin J. Bender, Patrick M. Fuller, Nirao M. Shah
Review
Immunology
Christina N. Heiss, Louise E. Olofsson
JOURNAL OF INNATE IMMUNITY
(2018)
Article
Cell Biology
Grace O. Mizuno, Yinxue Wang, Guilai Shi, Yizhi Wang, Junqing Sun, Stelios Papadopoulos, Gerard J. Broussard, Elizabeth K. Unger, Wenbin Deng, Jason Weick, Anita Bhattacharyya, Chao-Yin Chen, Guoqiang Yu, Loren L. Looger, Lin Tian
Article
Biochemistry & Molecular Biology
Cindy F. Yang, Michael C. Chiang, Daniel C. Gray, Mahalakshmi Prabhakaran, Maricruz Alvarado, Scott A. Juntti, Elizabeth K. Unger, James A. Wells, Nirao M. Shah
Article
Endocrinology & Metabolism
Alison S. Reed, Elizabeth K. Unger, Louise E. Olofsson, Merisa L. Piper, Martin G. Myers, Allison W. Xu
Article
Endocrinology & Metabolism
Louise E. Olofsson, Bob Olsson, Theodore Lystig, Peter Jacobson, Margareta Jernas, Kajsa Sjoholm, Anders Gummesson, Lars Sjostrom, Per Eriksson, Anders Hamsten, Laura P. Hale, Dag S. Thelle, Bjorn Carlsson, Lena M. S. Carlsson
METABOLISM-CLINICAL AND EXPERIMENTAL
(2010)
Editorial Material
Multidisciplinary Sciences
Patrick Scheerer
Article
Neurosciences
Gerard Joey Broussard, Yajie Liang, Marina Fridman, Elizabeth K. Unger, Guanghan Meng, Xian Xiao, Na Ji, Leopoldo Petreanu, Lin Tian
NATURE NEUROSCIENCE
(2018)
Article
Multidisciplinary Sciences
Louise E. Olofsson, Elizabeth K. Unger, Clement C. Cheung, Allison W. Xu
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Article
Biochemistry & Molecular Biology
Ara Koh, Antonio Molinaro, Marcus Stahlman, Muhammad Tanweer Khan, Caroline Schmidt, Louise Manneras-Holm, Hao Wu, Alba Carreras, Heeyoon Jeong, Louise E. Olofsson, Per-Olof Bergh, Victor Gerdes, Annick Hartstra, Maurits de Brauw, Rosie Perkins, Max Nieuwdorp, Goran Bergstrom, Fredrik Backhed
Article
Biochemistry & Molecular Biology
Audrey Poupeau, Christian Garde, Karolina Sulek, Kiymet Citirikkaya, Jonas T. Treebak, Manimozhiyan Arumugam, David Simar, Louise E. Olofsson, Fredrik Backhed, Romain Barres
Article
Endocrinology & Metabolism
Christina N. Heiss, Louise E. Olofsson
JOURNAL OF NEUROENDOCRINOLOGY
(2019)
Article
Cell Biology
Christina N. Heiss, Louise Manneras-Holm, Ying Shiuan Lee, Julia Serrano-Lobo, Anna Hakansson Gladh, Randy J. Seeley, Daniel J. Drucker, Fredrik Backhed, Louise E. Olofsson
Summary: Mice lacking a microbiota are protected from diet-induced obesity. Depletion of gut microbiota attenuates diet-induced hypothalamic inflammation and enhances leptin sensitivity through GLP-1R-dependent mechanisms.