Article
Medicine, Research & Experimental
Tony Eight Lin, Min-Wu Chao, Wei-Chun HuangFu, Huang-Ju Tu, Zhao-Xiang Peng, Chih-Jou Su, Tzu-Ying Sung, Jui-Hua Hsieh, Cheng-Chung Lee, Chia-Ron Yang, Shiow-Lin Pan, Kai-Cheng Hsu
Summary: DYRK1A dysregulation is linked to various diseases, including neurodegenerative diseases like Alzheimer's. A novel selective small-molecule inhibitor targeting DYRK1A was identified through structure-based virtual screening, showing potential for alleviating tau protein aggregation in neurodegenerative pathologies.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Estelle Deboever, Alessandra Fistrovich, Christopher Hulme, Travis Dunckley
Summary: With the increasing aging population, finding therapeutic solutions for age-related diseases becomes crucial. Kinases play a pivotal role in human health and represent promising targets for drug development. DYRK1A, a protein implicated in various human diseases, has attracted significant attention for its potential therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L. Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung
Summary: This study reveals the role of CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, and suggests CK2 inhibition as a potential immunotherapeutic approach for treating cancer.
Article
Plant Sciences
Miri Choi, Ae-kyeong Kim, Youngwook Ham, Joo-Youn Lee, Daeyong Kim, Ansook Yang, Min Ju Jo, Eunyoung Yoon, Jung-Nyoung Heo, Sang-Bae Han, Min-Hyo Ki, Kyu-Sun Lee, Sungchan Cho
Summary: Aristolactam BIII, a natural product derived from herbal plants, was identified as a novel DYRK1A inhibitor with therapeutic potential for DS-related pathological conditions.
Article
Chemistry, Multidisciplinary
Liyun Zhao, Xuan Xiong, Li Liu, Qi Liang, Rongsheng Tong, Xuanlin Feng, Lan Bai, Jianyou Shi
Summary: This paper reviews recent discoveries of DYRK1A inhibitors and their structure-activity relationship, aiming to provide a theoretical basis for the development of DYRK1A inhibitors.
CHINESE CHEMICAL LETTERS
(2022)
Article
Virology
Ailyn C. Ramon, Om Basukala, Paola Massimi, Miranda Thomas, Yasser Perera, Lawrence Banks, Silvio E. Perea
Summary: This study investigated the physical interaction of CIGB-300 with HPV-E7 and its impact on CK2-mediated phosphorylation. The findings revealed that CIGB-300 binds to the N terminal region of E7 proteins of the HPV-16 type, reducing CK2-mediated phosphorylation of E7 and its binding to pRB. However, targeting of E7 phosphorylation by CIGB-300 seems to be dispensable for inducing cell death in HPV-18 cervical cancer-derived cells.
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease with no effective treatments. People with Down syndrome (DS) have an increased risk of AD, and DYRK1A may be a potential therapeutic target. Through studying Drosophila models, it was found that the DYRK1A inhibitor PST-001 can improve the pathological processes caused by AD and DS-associated genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease, a common neurodegenerative disease with no cure, is more prevalent in Down syndrome patients due to potential genetic factors. Research has shown that targeting DYRK1A gene with medication can reduce neurodegeneration caused by AD and DS-related genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Editorial Material
Pharmacology & Pharmacy
Marco P. Licciardello, Paul Workman
Summary: Casein kinase 2, a potential therapeutic target in cancer due to its high expression, did not exhibit broad antiproliferative activity in cancer cells when targeted by the new inhibitor SGC-CK2-1, developed by Wells and colleagues.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Xinzeyu Yi, Zhi Cao, Ying Yuan, Wen Li, Xinyue Cui, Zilin Chen, Xiang Hu, Aixi Yu
Summary: Osteosarcoma is a common malignancy of the skeletal system with poor prognosis and high recurrence rates. The overexpression of PIM1 kinase in OS has been targeted for the development of a novel near-infrared imaging and targeted therapeutic agent, QCAiCy7d, which showed promising results in vitro and vivo. This new conjugate has potential for precise tumor imaging and targeted treatment.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Cell Biology
Agata Barzowska, Barbara Pucelik, Katarzyna Pustelny, Alex Matsuda, Alicja Martyniak, Jacek Stepniewski, Anna Maksymiuk, Maciej Dawidowski, Ulli Rothweiler, Jozef Dulak, Grzegorz Dubin, Anna Czarna
Summary: This study demonstrates the efficacy of a set of small molecule inhibitors of DYRK1A kinase in promoting beta-cell proliferation, enhancing long-term insulin secretion, and balancing glucagon level in human islets. The compounds show significantly more pronounced effects compared to harmine and hold considerable promise for regenerative medicine in the treatment of T1DM and T2DM.
Article
Biochemistry & Molecular Biology
Mihaela-Liliana Tintas, Ludovic Peauger, Florent Alix, Cyril Papamicael, Thierry Besson, Jana Sopkova-de Oliveira Santos, Vincent Gembus, Vincent Levacher
Summary: The DYRK family of protein kinases, including DYRK1A and CLK1, are potential therapeutic targets for neurodegenerative diseases such as Alzheimer's disease. In this study, a new class of dihydroquinolines that inhibit hDYRK1A and hCLK1 in the nanomolar range are reported. The most potent inhibitor also exhibits antioxidant and radical scavenging properties, which are relevant in the context of Alzheimer's disease. Drug-likeness and molecular docking studies of these inhibitors are discussed.
Article
Virology
Ailyn C. Ramon, George Perez, Evelin Caballero, Mauro Rosales, Daylen Aguilar, Dania Vazquez-Blomquist, Yassel Ramos, Arielis Rodriguez-Ulloa, Viviana Falcon, Maria Pilar Rodriguez-Molto, Ke Yang, Yasser Perera, Silvio E. Perea
Summary: CIGB-325 shows antiviral activity against bovine coronavirus in vitro and interacts physically with viral proteins and a group of CK2 cellular substrates.
Article
Biology
Katrina Kildey, Neha S. Gandhi, Katherine B. Sahin, Esha T. Shah, Eric Boittier, Pascal H. G. Duijf, Christopher Molloy, Joshua T. Burgess, Sam Beard, Emma Bolderson, Amila Suraweera, Derek J. Richard, Kenneth J. O'Byrne, Mark N. Adams
Summary: Platinum-based chemotherapy is the mainstay of treatment for NSCLC, but resistance is a major issue. Research shows that CDCA3 levels correlate with sensitivity to platinum agents in NSCLC tumors, and inhibition of CK2 can increase CDCA3 levels and enhance sensitivity to platinum agents.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Malini Rammohan, Ethan Harris, Rahul S. Bhansali, Emily Zhao, Loretta S. Li, John D. Crispino
Summary: DYRK1A is an important enzyme that plays a crucial role not only in Down syndrome and neurodegenerative diseases, but also in cancer by regulating various biological processes. It acts as both an oncogene and a tumor suppressor depending on the cellular context.
Article
Cell Biology
Francesca Zonta, Christian Borgo, Camila Paz Quezada Meza, Ionica Masgras, Andrea Rasola, Mauro Salvi, Lorenzo A. Pinna, Maria Ruzzene
Summary: CK2, an overexpressed Ser/Thr protein kinase in many cancers, plays a crucial role in the uncontrolled proliferation, motility, and survival of cancer cells. This study reveals that both CK2 alpha and alpha' isoforms contribute to cell proliferation, survival, and tumorigenicity, with a prominent role for CK2 alpha in tumor metabolism.
Article
Chemistry, Medicinal
Christian Borgo, Luca Cesaro, Tsuyoshi Hirota, Keiko Kuwata, Claudio D'Amore, Thomas Ruppert, Renata Blatnik, Mauro Salvi, Lorenzo A. Pinna
Summary: CK2, a protein kinase with pleiotropic functions, is implicated in global human pathologies, particularly cancer. Selective inhibitors like CX4945 and GO289 show promise in controlling the CK2-dependent phosphoproteome.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Maria Teresa Valenti, Alessandro Matte, Enrica Federti, Mark Puder, Lorenzo Anez-Bustillos, Michela Deiana, Samuele Cheri, Arianna Minoia, Carlo Brugnara, Maria Luisa Di Paolo, Luca Dalle Carbonare, Lucia De Franceschi
Summary: Sickle cell disease is a genetic disorder causing chronic anemia and organ damage. Study shows that Omega-3 fatty acids can improve osteogenesis, reduce inflammation, and promote adipose tissue transformation, offering new insights for the treatment of SBD.
Article
Biochemistry & Molecular Biology
Erica Gentilin, Alice Cani, Edi Simoni, Milvia Chicca, Maria Luisa Di Paolo, Alessandro Martini, Laura Astolfi
Summary: The study highlights the importance of reactive oxygen species (ROS) in hearing loss pathologies and the development of an in vitro model using the OC-k3 cell line to study the effects of ROS on inner ear cells. High concentrations of hydrogen peroxide resulted in reduced cell viability, activation of apoptosis/necrosis, and alteration of cell morphology, cell cycle progression, and antioxidant defenses. This model could be valuable for investigating inner ear oxidative stress and potential countermeasures.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Mariafrancesca Hyeraci, Laura Agnarelli, Luca Labella, Fabio Marchetti, Maria Luisa Di Paolo, Simona Samaritani, Lisa Dalla Via
Summary: Resistance to cisplatin limits its usefulness as an anticancer drug. This study describes the synthesis and characterization of two new platinum complexes and demonstrates their potential in overcoming cisplatin resistance in cancer cells. The complexes exhibited poor ability to platinate DNA but showed significant intracellular accumulation. Mechanistic studies revealed their ability to inhibit DNA relaxation and activate the apoptotic pathway. Comparison with related complexes provides insights into the resistance phenotype.
Article
Chemistry, Medicinal
Rino Ragno, Anna Minarini, Eleonora Proia, Antonini Lorenzo, Andrea Milelli, Vincenzo Tumiatti, Marco Fiore, Pasquale Fino, Lavinia Rutigliano, Rossella Fioravanti, Tomoaki Tahara, Elena Pacella, Antonio Greco, Gianluca Canettieri, Maria Luisa Di Paolo, Enzo Agostinelli
Summary: Polyamines play important roles in regulating cell growth, proliferation, and death. Accumulated polyamines can be utilized as a strategy to inhibit tumor progression. This study focuses on the design and synthesis of spermine analogues, and explores their interaction with enzyme BSAO to understand the biochemical kinetics. By developing three-dimensional quantitative structure-activity relationship models, this study provides a basis for future design and synthesis of polyamine BSAO substrates for oxidative stress-induced chemotherapy.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Graziano Rilievo, Alessandro Cecconello, Simone Molinari, Andrea Venerando, Lavinia Rutigliano, Gayathri T. Govardhan, Dinusha H. Kariyawasam, Ruth J. Arusei, Lucio Zennaro, Maria L. Di Paolo, Enzo Agostinelli, Fabio Vianello, Massimiliano Magro
Summary: Protein-nanoparticle hybrids with emerging biological properties were created by immobilizing bovine serum amine oxidase onto magnetic nanomaterial. The immobilized BSAO showed sensitive response to pH variations, leading to modulation of its activity. This study highlights the significance of protein-nanoparticle conjugation in modulating biological functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Eleonora Colombo, Davide Andrea Coppini, Laura Polito, Umberto Ciriello, Giuseppe Paladino, Mariafrancesca Hyeraci, Maria Luisa Di Paolo, Giulia Nordio, Lisa Dalla Via, Daniele Passarella
Summary: Cannabidiol (CBD), a compound found in Cannabis plants, is shown to be an effective inducer in the formation of nanoparticles. These nanoparticles, formed through solvent displacement, exhibit monodisperse and stable structures. They show low micromolar range cytotoxicity on human tumor cell lines, with the involvement of paclitaxel confirmed in the most effective nanoparticle (NP 8B) through further biological assays.
Article
Biochemistry & Molecular Biology
Lorenzo Badenetti, Rosa Manzoli, Michela Rubin, Giorgio Cozza, Enrico Moro
Summary: Among cytoprotective mechanisms, eukaryotic cells rely on the Nrf2 transcription factor to initiate a complex transcriptional program during biological stressors, including oxidative stress. Nrf2 has recently been found to play a crucial role in various research fields, such as cancer, inflammatory disorders, and age-related neurological diseases. In this study, a novel Nrf2/ARE pathway biosensor fish was generated and characterized, demonstrating spatiotemporal expression during early development. This transgenic fish shows responsiveness to Nrf2 pathway modulators and Edaravone, which has not been seen in any live transgenic fish models before. The activated reporter in this fish is also shown to be faithful during fin regeneration and slightly affected in a glucocerebrosidase morphant zebrafish model. Therefore, this innovative transgenic fish can serve as a valuable tool for studying zebrafish models of human diseases and primary high-throughput drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Antonia I. Antoniou, Giulia Nordio, Maria Luisa Di Paolo, Eleonora Colombo, Beatrice Gaffuri, Laura Polito, Arianna Amenta, Pierfausto Seneci, Lisa Dalla Via, Dario Perdicchia, Daniele Passarella
Summary: 2-Hydroxyoleic acid (6, 2OHOA), a nontoxic antitumor drug, was used to form nanoparticles (NPs) in water and enhance cell penetration and drug release. The synthesized NP formulations showed antiproliferative activity against human tumor cell lines. The disulfide-containing linker in the nanoformulations promoted cellular effects.
Article
Biochemistry & Molecular Biology
Filippo Basagni, Maria Luisa Di Paolo, Giorgio Cozza, Lisa Dalla Via, Francesca Fagiani, Cristina Lanni, Michela Rosini, Anna Minarini
Summary: Oxidative stress and neuroinflammation are important factors in neurodegenerative disorders, and the antidiabetic drug pioglitazone has promising neuroprotective properties. By enriching pioglitazone with antioxidant properties, a caffeic acid derivative 2 was found to be a potent and selective inhibitor of MAO-B and an activator of the Nrf2 pathway, reducing oxidative stress.
Article
Biochemistry & Molecular Biology
Giulia Nordio, Francesco Piazzola, Giorgio Cozza, Monica Rossetto, Manuela Cervelli, Anna Minarini, Filippo Basagni, Elisa Tassinari, Lisa Dalla Via, Andrea Milelli, Maria Luisa Di Paolo
Summary: Monoamine oxidases (MAOs) have been widely studied in neurological diseases, but recent research has discovered their potential role in certain types of cancer. This study identified novel MAO inhibitors with antiproliferative activity, suggesting their potential as anticancer agents.
Article
Chemistry, Inorganic & Nuclear
Anna Farasat, Luca Labella, Maria Luisa Di Paolo, Lisa Dalla Via, Simona Samaritani
Summary: This study synthesized a series of new N-acyclic carbene and isonitrile complexes of platinum(II). Among them, NAC derivatives showed a moderate cytotoxic effect on MSTO-211H cells.
Article
Chemistry, Medicinal
Rino Ragno, Anna Minarini, Eleonora Proia, Antonini Lorenzo, Andrea Milelli, Vincenzo Tumiatti, Marco Fiore, Pasquale Fino, Lavinia Rutigliano, Rossella Fioravanti, Tomoaki Tahara, Elena Pacella, Antonio Greco, Gianluca Canettieri, Maria Luisa Di Paolo, Enzo Agostinelli
Summary: Natural polyamines play important roles in regulating cell growth and proliferation, as well as in modulating cell death pathways. This study investigated the cytotoxic effects of polyamine accumulation, particularly with the use of bovine serum amine oxidase (BSAO) enzyme, which showed promise in inhibiting tumor progression. New spermine analogues were synthesized and evaluated, and a mixed structure-based and ligand-based approach was applied to analyze the binding modes of BSAO-polyamine complexes. The developed three-dimensional quantitative structure-activity relationship models provide a foundation for future design and synthesis of BSAO substrates with potential applications in oxidative stress-induced chemotherapy.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee
Summary: Glutaredoxin 3 (Grx3) is a redox protein that maintains structural integrity and glutathione (GSH) binding capabilities across different temperatures. This study investigates the roles of specific bonds in Grx3's structure and function, and how psychrophilic Grx3 variants adapt to cold environments. The highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the structure and catalytic activity of Grx3. Psychrophilic variants of Grx3 have adapted to cold environments by reducing GSH binding and increasing structural flexibility.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Amanda Lais de Souza Coto, Arthur Alexandre Pereira, Sabrina Dorta Oliveira, Milene Nobrega de Oliveira Moritz, Arthur Moraes Franco da Rocha, Paulo Roberto Dores-Silva, Noeli Soares Melo da Silva, Ana Rita de Araujo Nogueira, Lisandra Marques Gava, Thiago Vagas Seraphim, Julio Cesar Borges
Summary: J-domain proteins form a large molecular chaperone family involved in proteostasis processes, with hDjC20 playing a vital role in mitochondria and being heavily influenced by the presence of Zn+2.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Meiling Zhang, Jiaxiang Zhang, Yan Liang, Shicheng Tian, Shuyang Xie, Tong Zhou, Qin Wang
Summary: This study determined the crystal structures of RGLG2 VWA domain in Arabidopsis thaliana, revealing that Ca2+ ions act as regulators and affect the conformational change of RGLG2-VWA domain.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Alexandra Bork, Sander H. J. Smits, Lutz Schmitt
Summary: This study reveals the structure and calcium ion binding properties of CBL1 protein, and proposes a binding model of CBL1 for Ca2+. Additionally, it provides preliminary insights into the formation of the dimer interface of CBL1.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Evgeniia V. Leisi, Andrey V. Moiseenko, Sofia S. Kudryavtseva, Denis V. Pozdyshev, Vladimir I. Muronetz, Lidia P. Kurochkina
Summary: The pathogenesis of prion diseases involves the transformation of prion protein into an insoluble form. This study found that two phage chaperonins can promote the fibrillation of prion protein in an ATP-dependent manner, resulting in the formation of less toxic large clusters. These fibrils differ in morphology and properties from those formed spontaneously in acidic pH with denaturants.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Gaurab Chowdhury, Saroj Biswas, Yuthika Dholey, Puja Panja, Sumit Das, Subrata Adak
Summary: Magnesium is an important divalent cation for regulating enzyme activity. The binding of Mg2+ through the PAS domain inhibits phosphoglycerate kinase (PGK) activity in LmPAS-PGK at neutral pH, but PGK activity is derepressed at acidic pH. Mutation studies revealed that the Asp-4 residue is crucial for Mg2+ binding at neutral pH.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Shima Ghaedizadeh, Majid Zeinali, Bahareh Dabirmanesh, Behnam Rasekh, Khosrow Khajeh, Ali Mohammad Banaei-Moghaddam
Summary: Implementing hyperthermostable carbonic anhydrases into CO2 capture and storage technologies can increase the rate of CO2 absorption from industrial flue gases. This study successfully improved the thermostability of a known hyperthermostable carbonic anhydrase through rational engineering of a single-point mutation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Khaled A. Elnahriry, Dorothy C. C. Wai, Lauren M. Ashwood, Muhammad Umair Naseem, Tibor G. Szanto, Shaodong Guo, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Sea anemone venom contains a peptide called Tst2, which shows sequence similarity to peptides that interact with various ion channels. Recombinant Tst2 was successfully produced and its structure and function were studied. The results showed that Tst2 is an inhibitor of the TRPV1 channel.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)