Article
Endocrinology & Metabolism
Jinpeng Wu, Zengqi Tan, Hongjiao Li, Meixuan Lin, Yazhuo Jiang, Liang Liang, Qilong Ma, Junjie Gou, Lulu Ning, Xiang Li, Feng Guan
Summary: Melatonin inhibits the elevated O-GlcNAc levels in bladder cancer cells, leading to reduced proliferation and increased apoptosis. This effect is achieved by decreasing glucose uptake, metabolic flux, and CDK5 expression, ultimately suppressing tumor growth.
JOURNAL OF PINEAL RESEARCH
(2021)
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
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)
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
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)
Review
Biochemistry & Molecular Biology
Pawel Lukasik, Michal Zaluski, Izabela Gutowska
Summary: Cyclin-dependent kinases are crucial in various cellular processes and their dysregulation can lead to diseases, making them potential drug targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Takahisa Hirokawa, Taeko Horie, Yurie Fukiyama, Masashi Mimura, Shinji Takai, Teruyo Kida, Hidehiro Oku
Summary: The study identified that the overactivation of Cdk5 is associated with the development of tauopathies. Roscovitine, a Cdk5 inhibitor, reduces the phosphorylation level of tau protein and mitigates the pathologic phosphorylation of tau by inhibiting the calpain signaling pathway, thereby alleviating the degeneration of RGCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Akhtar Atiya, Shivani Batra, Taj Mohammad, Nasser M. Alorfi, Waleed Al Abdulmonem, Fahad A. Alhumaydhi, Ghulam Md Ashraf, Saleh S. Baeesa, Abdelbaset Mohamed Elasbali, Moyad Shahwan
Summary: This study identified two potential CDK5 inhibitors through virtual screening from a herbal library. These compounds showed significant binding to CDK5's ATP-binding pocket. These findings are important for treating complex diseases such as neurodegeneration and tumors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Oncology
Elena Garralda, Alison M. Schram, Philippe L. Bedard, Gary K. Schwartz, Eunice Yuen, Samuel C. McNeely, Silvia Ribeiro, Jason Cunningham, Yi Wang, Arantxa Urunuela, Xiaojian Xu, Patricia LoRusso
Summary: LY3405105 is a promising CDK7 inhibitor with good bioavailability and selectivity. However, the clinical trial showed limited efficacy and no plans for further development. The MTD of LY3405105 monotherapy was determined to be 20 mg QD.
Review
Biochemistry & Molecular Biology
Jorrit M. Enserink, Pierre Chymkowitch
Summary: Cdk1 is a master regulator of the cell cycle, controlling progression through different phases. It also directly regulates RNA polymerase activity, which is important for protein synthesis and meeting cellular demands. This regulation promotes cell cycle entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shunyao Liu, Bo Li, Danna Ma, Yuejia Tao, Jiang Song, Li Bao, Guoqing Zhang, Hongyan Luo, Shilu Cao, Jing E, Yali Zheng
Summary: This study investigated the role of a CDK5 inhibitor (TFP5) in islet beta-cell damage under diabetic conditions by regulating the expression of CDK5 in vitro and in vivo. CDK5 was upregulated under high glucose conditions in vivo and in vitro, which resulted in inflammation, oxidative stress, and apoptosis of islet beta-cells, thereby decreasing insulin secretion. However, TFP5 treatment inhibited the overexpression of CDK5; reduced the inflammatory response, oxidative stress, and apoptosis of islet beta cells; and restored insulin secretion.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Biochemistry & Molecular Biology
Chen Chen, Jian-Wen Liu, Ling-Li Guo, Feng Xiong, Xiao-Qian Ran, Ya-Rong Guo, Yong-Gang Yao, Xiao-Jiang Hao, Rong-Can Luo, Yu Zhang
Summary: Three novel monoterpenoid indole alkaloid dimers (kopoffines A-C) and nine known alkaloids were isolated and identified from the fruits of Kopsia arborea Blume. Kopoffines A-C exhibited significant inhibition against cyclin-dependent kinase 5 and reduced the levels of phosphorylated Tau, which are involved in the formation of neurofibrillary tangles. These findings may have implications for the development of therapeutics for related diseases.
Article
Oncology
Satu Pallasaho, Aishwarya Gondane, Anni Kuivalainen, Samuel Girmay, Siver Moestue, Massimo Loda, Harri M. Itkonen
Summary: The study reveals that CDK7 and CDK9 are highly active in castration-resistant prostate cancer (CRPC) cells, and inhibiting these kinases can effectively suppress the proliferation of CRPC cells.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Gabor Zsurka, Maximilian L. T. Appel, Maximilian Nastaly, Kerstin Hallmann, Niels Hansen, Daniel Nass, Tobias Baumgartner, Rainer Surges, Gunther Hartmann, Eva Bartok, Wolfram S. Kunz
Summary: This study reports on a family with three affected individuals exhibiting symptoms resembling a neurodevelopmental disorder. Whole-exome sequencing identified a homozygous stop-gain mutation in the BATF2 gene, which is predominantly expressed in macrophages and monocytes and plays a role in modulating pro-inflammatory responses. Transcriptome analysis showed altered expression of interferon-stimulated genes and elevated responses to innate immune stimuli in the patients' blood. These findings suggest that BATF2 may be a novel disease-associated gene candidate for severe epilepsy and mental retardation related to dysregulation of immune responses, highlighting the importance of neuroinflammation in epilepsy.
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
Biotechnology & Applied Microbiology
Wilaiwan Sriwimol, Pornprot Limprasert
BIOMED RESEARCH INTERNATIONAL
(2018)
Article
Biochemistry & Molecular Biology
Chuphong Thongnak, Areerat Hnoonual, Duangkamol Tangviriyapaiboon, Suchaya Silvilairat, Apichaya Puangpetch, Ekawat Pasomsub, Wasun Chantratita, Pornprot Limprasert, Chonlaphat Sukasem
INTERNATIONAL JOURNAL OF GENOMICS
(2018)
Article
Genetics & Heredity
Areerat Hnoonual, Potchanapond Graidist, Supika Kritsaneepaiboon, Pornprot Limprasert
FRONTIERS IN GENETICS
(2019)
Article
Clinical Neurology
Utcharee Intusoma, Chompunut Na Nakorn, Thirachit Chotsampancharoen
PEDIATRIC NEUROLOGY
(2019)
Article
Medicine, General & Internal
Wikrom Wongpaiboonwattana, Oradawan Plong-On, Areerat Hnoonual, Pornprot Limprasert
Article
Genetics & Heredity
Areerat Hnoonual, Phawin Kor-anantakul, Chariyawan Charalsawadi, Juthamas Worachotekamjorn, Pornprot Limprasert
Summary: This study identified a case of ASD with maternal UPD of chromosome 15, consistent with Angelman syndrome. The patient’s clinical features did not match classic Angelman syndrome, highlighting the importance of testing for Angelman syndrome in ASD patients with unknown etiology.
FRONTIERS IN GENETICS
(2021)
Article
Biotechnology & Applied Microbiology
Areerat Hnoonual, Charunee Jankittunpaiboon, Pornprot Limprasert
Summary: This study analyzed the FMR1 gene CGG repeat sizes in Thai autistic patients and found similar distributions between ASD and normal control groups. No full mutations or premutations were found, but intermediate alleles were present in approximately 1% of ASD patients. Further studies are needed to investigate other mutations in the FMR1 gene for a better understanding of FXS prevalence in Thai ASD patients.
BIOMED RESEARCH INTERNATIONAL
(2021)
Article
Pediatrics
Chariyawan Charalsawadi, Sasipong Trongnit, Kanoot Jaruthamsophon, Juthamas Wirojanan, Somchit Jaruratanasirikul, Anupong Nitiruangjaras, Pornprot Limprasert
Summary: This study found a possible genetic association between pilomatricoma and the CTNNB1 gene, but did not detect this genetic feature in a patient with tetrasomy 9p syndrome. The expression of beta-catenin and bcl2 proteins in pilomatricoma was also not observed in this patient.
INTERNATIONAL JOURNAL OF PEDIATRICS
(2021)
Article
Public, Environmental & Occupational Health
Utcharee Intusoma, Rapeepat Thewamit, Titaporn Thamcharoenvipas, Puttichart Khantee
Summary: This study conducted the first epidemiological research on Haemophilus influenzae (Hi) type b (Hib) before the implementation of the Hib immunisation programme. The study found that the incidence of Hi disease in children was lower than previously speculated, with pneumonia being the most common clinical form, followed by meningitis and sepsis. The infant case fatality rate was higher than in other age groups, and the primary cause of death in infants was sepsis.
TROPICAL MEDICINE & INTERNATIONAL HEALTH
(2022)
Review
Genetics & Heredity
Chariyawan Charalsawadi, Somchit Jaruratanasirikul, Areerat Hnoonual, Aussanai Chantarapong, Pornsiri Sangmanee, Sasipong Trongnit, Natini Jinawath, Pornprot Limprasert
Summary: Chimerism is a rare genetic phenomenon in humans, and only a few cases have been reported with both trisomy 21 and a normal karyotype. In this case report, a patient with ambiguous genitalia and no features of Down syndrome or other malformations was found to have a chimera with a chi 47,XY,+21/46,XX karyotype. Analyses revealed that the extra chromosome 21 was paternally derived, and meiosis I nondisjunction likely occurred during spermatogenesis. The mechanism of chimerism in this case was likely the fertilization of two spermatozoa, one with an ovum and the other with the second polar body.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, General & Internal
Wikrom Wongpaiboonwattana, Areerat Hnoonual, Pornprot Limprasert
Summary: This study identified an association between the 19-bp insertion allele of the DBH gene and ASD, particularly in families with male participants. This suggests a potential link between the DBH gene and ASD.
MEDICINA-LITHUANIA
(2022)
Article
Clinical Neurology
Thara Tunthanathip, Sanguansin Ratanalert, Sakchai Sae-heng, Thakul Oearsakul, Ittichai Sakaruncchai, Anukoon Kaewborisutsakul, Thirachit Chotsampancharoen, Utcharee Intusoma, Amnat Kitkhuandee, Tanat Vaniyapong
JOURNAL OF NEUROSCIENCES IN RURAL PRACTICE
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
P. Limprasert, A. Hnoonual, J. Worachotekamjorn
EUROPEAN JOURNAL OF HUMAN GENETICS
(2019)
Meeting Abstract
Biochemistry & Molecular Biology
P. Limprasert, A. Hnoonual, P. Graidist
EUROPEAN JOURNAL OF HUMAN GENETICS
(2018)
Meeting Abstract
Clinical Neurology
John Vincent, Ricardo Harripaul, Larysa Santavy, Amy NcNaughton, Kirti Mittal, Nasim Vasli, Anna Mikhailov, Cameron Henry, Melissa Hudson, Christian Windpassinger, James Stavropoulos, Melissa Carter, Pornprot Limprasert, Muhammad Ayub, Xudong Liu
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2017)
Article
Clinical Neurology
Karlijn Bouman, Jeroen L. M. van Doorn, Jan T. Groothuis, Peter J. Wijkstra, Baziel G. M. van Engelen, Corrie E. Erasmus, Jonne Doorduin, Nicol C. Voermans
Summary: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Oliviero Bruni, Maria Breda, Emanuela Malorgio, Paolo Brambilla, Flavia Ceschin, Andrea Di Pilla, Maurizio Elia, Raffaele Ferri
Summary: This study aimed to describe the use of melatonin by Italian pediatricians in healthy children with chronic insomnia. The results showed that a high percentage of pediatricians prescribed melatonin, especially in children aged 1-2 years. The most common dosage was 1 mg/day and it was usually recommended to be taken 30 minutes before bedtime. Melatonin was often combined with sleep hygiene and was found to be effective in reducing difficulties falling asleep.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Lucie Sedlackova, Katalin Sterbova, Marketa Vlckova, Pavel Seeman, Jana Zarubova, Petr Marusic, Pavel Krsek, Hana Krijtova, Alena Musilova, Petra Lassuthova
Summary: In this study, whole exome sequencing (WES) was performed to identify causal variants for developmental and epileptic encephalopathies (DEEs) in patients whose genetic diagnosis was not determined by gene panel testing. The results showed that WES can successfully identify disease-causing variants, even after inconclusive gene panel testing. Detailed clinical evaluations and phenotype-genotype correlation studies were conducted to better understand the rare subtypes of DEEs.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)