Article
Biochemistry & Molecular Biology
Lifei Wang, Dan Lu, Yan Wang, Xiaoyan Xu, Peihua Zhong, Zhiyong Yang
Summary: Multiple short molecular dynamics simulations and calculations were used to investigate the binding selectivity mechanism of inhibitors X64, X3A, and 4 AU towards CDK2 and CDK6. The study found that CDK6 has stronger local structural and global flexibility compared to CDK2. The calculated binding free energies showed that the compensation between binding enthalpy and entropy is a key factor driving selectivity of inhibitors towards CDK2 over CDK6.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Yanting Zhou, Xiandeng Li, Peifang Luo, Huiting Chen, Yan Zhou, Xueting Zheng, Yuan Yin, Haoche Wei, Hongji Liu, Wen Xia, Mingsong Shi, Xiaoan Li
Summary: CDK4/6 is a crucial player in various cancers and a potential target for anticancer drugs. The interaction between abemaciclib and human CDK6 was studied, and C2231-A was identified as a promising candidate compound with significant inhibitory effects on human breast cancer cell lines.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Neurosciences
Yan-Yan Zhang, Fei Liu, Jiu Lin, Yue-Ling Li, Zhong-Han Fang, Cheng Zhou, Chun-Jie Li, Jie-Fei Shen
Summary: Neuropathic and inflammatory pain pose major challenges in clinical practice. This study explores the roles of NMDAR and CaMKII in orofacial pain and reveals new molecular signaling pathways involved in peripheral and central sensitization. The findings suggest that targeting NR2B and CaMKII may be beneficial for the treatment of orofacial allodynia.
BRAIN RESEARCH BULLETIN
(2022)
Article
Biochemistry & Molecular Biology
Mateusz Kciuk, Adrianna Gieleci, Somdutt Mujwar, Mariusz Mojzych, Renata Kontek
Summary: The cyclin-dependent kinase (CDK) family plays a critical role in regulating transcription and cell-cycle progression. Recent studies have revealed their involvement in DNA damage response (DDR) and repair, impacting the fidelity of cell division and maintenance of genomic integrity.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Pharmacology & Pharmacy
Rita Borzsei, Eva Borbely, Boglarka Kantas, Lina Hudhud, Adam Horvath, Eva Szoke, Csaba Hetenyi, Zsuzsanna Helyes, Erika Pinter
Summary: Due to limited effectiveness and serious side effects of conventional and adjuvant analgesics, developing novel pain killers for chronic neuropathic and inflammatory pain conditions is a challenge. This study found that TT-232, a cyclic heptapeptide, binds to SST4 and shows analgesic and anti-inflammatory effects in chronic pain models. The activation of SST4 by TT-232 indicates its potential as a new drug for pain management.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Shivani Batra, Shagufta Jahan, Anam Ashraf, Bandar Alharby, Talha Jawaid, Asimul Islam, Imtaiyaz Hassan
Summary: Cyclin-dependent kinase 5 (CDK5) is a serine/threonine-directed kinase primarily found in the brain that plays a crucial role in the development of the central nervous system. Recent research has shown that CDK5 is activated by specific cyclins, which regulate its expression and activity. This review examines the role of CDK5 in neurons, synaptic plasticity, DNA damage repair, and the cell cycle, highlighting its therapeutic potential as a target for neurodegenerative diseases. The structural features of CDK5 and its binding with designed inhibitors are also discussed, providing insights for the development of attractive strategies in therapeutic targeting.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Neurosciences
Manindra Nath Tiwari, Bradford E. Hall, Anh-Tuan Ton, Re Ghetti, Anita Terse, Niranjana Amin, Man-Kyo Chung, Ashok B. Kulkarni
Summary: CDK5 activation in human sensory neurons affects nociceptor activity through phosphorylation. It depolarizes the resting membrane potential and changes the shape of the action potential. The effect of a prostaglandin E2 and bradykinin cocktail on nociceptor activity is not significant in the CDK5 overexpressing group. These findings reveal the important role of CDK5 in chronic pain.
Article
Multidisciplinary Sciences
Assaf Alon, Jiankun Lyu, Joao M. Braz, Tia A. Tummino, Veronica Craik, Matthew J. O'Meara, Chase M. Webb, Dmytro S. Radchenko, Yurii S. Moroz, Xi-Ping Huang, Yongfeng Liu, Bryan L. Roth, John J. Irwin, Allan Basbaum, Brian K. Shoichet, Andrew C. Kruse
Summary: The study determined the crystal structure of sigma(2) receptor with roluperidone and PB28, identified new chemical compounds with higher affinities, and confirmed the role of sigma(2) receptor in pain perception, highlighting the potential for developing new pain treatments.
Article
Biochemistry & Molecular Biology
Haokun Cheng, Gengyu Pan, Na Zhou, Zengkang Zhai, Liuqing Yang, Huafan Zhu, Xing Cui, Peiyu Zhao, Hanfeng Zhang, Shaojun Li, Bo Yang, Yuan-Qing Jiang
Summary: The study identified that BnaCPK5 enhances drought stress tolerance by phosphorylating core ABA signaling components, ABF3 and ABF4, thus modulating the expression of RD29B, a well-known drought stress marker gene.
Article
Neurosciences
Li Lin, Xiaodong Liu, Xuejun Cheng, Yujing Li, Marla Gearing, Allan Levey, Xiaoli Huang, Ying Li, Peng Jin, Xuekun Li
Summary: In this study, the altered expression and misregulation of miR-650 in Alzheimer's disease (AD) brains were observed. Bioinformatic analysis predicted that miR-650 targets three AD-associated genes, and experimental confirmation showed that miR-650 significantly reduces their expression levels in vitro. Overexpression of miR-650 was shown to alter CDK5 levels and ameliorate AD pathologies in transgenic mice. These findings suggest that miR-650 influences AD pathogenesis through regulation of CDK5.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Qin Li, Yunqin Shen, Xingyue Guo, Yixuan Xu, Yuheng Mao, Yinfan Wu, Fang He, Caixia Wang, Yanqiu Chen, Yan Yang
Summary: Betanin can dose-dependently alleviate allergic asthma and upregulate the cAMP-PKA-CREB pathway. This study provides a novel nutritional strategy for the treatment of allergic asthma.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Neurosciences
Elia R. Lopez, Anibal Garza Carbajal, Jin Bin Tian, Alexis Bavencoffe, Michael X. Zhu, Carmen W. Dessauer, Edgar T. Walters
Summary: Recent research has shown that serotonin promotes ongoing activity in nociceptors through activation of the 5-HT4 receptor and downstream cAMP signaling. This finding provides new insights and potential therapeutic targets for the study of neuropathic pain.
Editorial Material
Chemistry, Medicinal
Mark Klein
Summary: Cyclin-dependent kinases (CDKs) have important roles in normal cells and can be targeted for cancer therapy. CDK4 inhibitors have been approved for advanced breast cancer treatment. However, the development of selective inhibitors for individual CDKs is challenging due to the highly conserved ATP-binding site.
Article
Biochemistry & Molecular Biology
Lin Yuan, Wanying Yi, Changyu Sun, Shuangshuang Ma, Jiali Wang, Saijuan Liu, Yijing Chen, Yuewen Chen, Yu Chen
Summary: Dendritic spines, the postsynaptic structures in neural circuitry, are regulated by EphB2 signaling, which involves the activation of CREB to modulate the expression of Annexin A1, ultimately impacting dendritic spine morphology.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Microbiology
Juri Kim, Eun-Ah Park, Mee Young Shin, Soon-Jung Park
Summary: This study investigated the functional roles of Giardia lamblia CDKs (GlCDKs) and their cognate cyclins. Using morpholino-mediated knockdown and coimmunoprecipitation, the functions of GlCDK1 and GlCDK2 were distinguished. GlCDK1 with Glcyclin 3977 plays a crucial role in flagellum formation and cell cycle control of G. lamblia, while GlCDK2 with Glcyclin 22394/6584 is involved in cell cycle control.
MICROBIOLOGY SPECTRUM
(2023)