Article
Cell Biology
Dong-gui Wu, Yu-na Wang, Ye Zhou, Han Gao, Bei Zhao
Summary: This study investigates the role of the PA28-regulated function of the proteasome in diabetes-induced oxidative damaged protein degradation. The results show that proteasome activity changes in the brains of diabetic rats and that PA28 is functionally involved in the regulation of proteasome activity. This suggests that abnormal protein turbulence in the diabetic brain could be explained by the proteasome-mediated degradation pathway.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Panfeng Tao, Shihao Wang, Seza Ozen, Pui Y. Lee, Jiahui Zhang, Jun Wang, Huan Han, Zhaohui Yang, Ran Fang, Wanxia Li Tsai, Huanming Yang, Erdal Sag, Rezan Topaloglu, Ivona Aksentijevich, Xiaomin Yu, Qing Zhou
Summary: OTULIN deficiency leads to activation of NF-κB and IFN-I signaling pathways, caused by dysregulated proteasomes due to the deubiquitinase activity of OTULIN. This suggests a crucial role of linear ubiquitination in regulating proteasome function and its link to autoinflammatory syndromes associated with proteasome dysfunction.
Review
Cell Biology
Satyendra Chandra Tripathi, Disha Vedpathak, Edwin Justin Ostrin
Summary: Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Immunoproteasomes, with inducible activity by inflammatory stimuli, play central roles in cancer, autoimmunity, and inflammation by altering the catalytic activity of the proteasome.Understanding the roles of immunoproteasome in different cancers offers insights into developing targeted therapies.
Article
Biochemistry & Molecular Biology
Rodrigo E. Caceres-Gutierrez, Marco A. Andonegui, Diego A. Oliva-Rico, Rodrigo Gonzalez-Barrios, Fernando Luna, Cristian Arriaga-Canon, Alejandro Lopez-Saavedra, Diddier Prada, Clementina Castro, Laurent Parmentier, Jose Diaz-Chavez, Yair Alfaro-Mora, Erick Navarro-Delgado, Eunice Fabian-Morales, Bao Tran, Jyoti Shetty, Yongmei Zhao, Nicolas Alcaraz, Carlos De la Rosa, Jose L. Reyes, Sabrine Hedouin, Florent Hube, Claire Francastel, Luis A. Herrera
Summary: The study reveals that proteasome inhibition leads to upregulation of repetitive RNAs, particularly affecting alpha-Satellite RNAs in cancer cells. The results show fluctuation of alpha-Satellite RNAs along the cell cycle and their interaction with members of the cohesin ring, suggesting a role in mitotic progression regulation.
Article
Chemistry, Applied
Bo Chen, Chang-Sheng Kuai, Jian-Xing Xu, Xiao-Feng Wu
Summary: A Mn(III)-promoted double carbonylation reaction using anilines and alkylborates or Hantzsch esters has been developed for the synthesis of alkyl alpha-ketoamides with excellent selectivity. The method provides a broad range of derivatives in moderate to good yields.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Medicine, General & Internal
Boranai Tychhon, Jesse C. Allen, Mayra A. Gonzalez, Idaly M. Olivas, Jonathan P. Solecki, Mehrshad Keivan, Vanessa V. Velazquez, Emily B. McCall, Desiree N. Tapia, Andres J. Rubio, Connor Jordan, David Elliott, Anna M. Eiring
Summary: This study found that the expression of PSMC1-6 subunits of the 19S proteasome is elevated in several cancers and is associated with worse prognosis. In AML patients, high expression of PSMC2-5 leads to worse outcomes.
FRONTIERS IN MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Xiao Wang, Shen Liu, Tao Yu, Senbo An, Ruoxian Deng, Xiaohua Tan, Janet Crane, Weixin Zhang, Dayu Pan, Mei Wan, Andrew Carr, Xu Cao
Summary: This study demonstrates that activating TGF-beta through integrin alpha v beta 6 is the mechanism behind tendinopathy, suggesting it as a potential therapeutic target.
Article
Multidisciplinary Sciences
Adrian C. D. Fuchs, Moritz Ammelburg, Joerg Martin, Ruth A. Schmitz, Marcus D. Hartmann, Andrei N. Lupas
Summary: Connectase is a sequence-specific protein ligase that catalyzes protein ligations at higher rates and yields with no side reactions compared to reference enzymes. Its recognition tag derived from MtrA enables the ligation of unrelated proteins, making it a versatile tool for various applications in protein engineering.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Food Science & Technology
Bong-Geum Jang, Jisun Lee, Boyoung Choi, Young Ho Koh, Min-Ju Kim
Summary: Resveratrol, a drug candidate for Alzheimer's disease, has shown beneficial effects in various models but may paradoxically increase Aβ production. This effect may be mediated by AMPK-proteasome signaling pathway.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Chemistry, Physical
Jiao Zhou, Xiaohong Sang, Juan Wang, Yan Xu, Jing An, Zhen Tao Chu, Arjun Saha, Arieh Warshel, Ziwei Huang
Summary: The covalent inhibition mechanism of an alpha-keto phenylamide inhibitor of the 20S proteasome was investigated in this study. Different reaction pathways were explored through calculations of noncovalent binding free energy and reaction free energy. The calculated results were validated by performing kinetic experiments, and the effects of the ionization states of Asp17 on the reaction were discussed. The results demonstrated the critical electrostatic effect of Asp17 in the active site of the 20S proteasome.
Article
Cell Biology
Marianna Kapetanou, Tobias Nespital, Luke S. Tain, Andre Pahl, Linda Partridge, Efstathios S. Gonos
Summary: As organisms age, proteostasis is disrupted, leading to the accumulation of damaged and aggregated proteins. The FoxO1 transcription factor is shown to directly regulate proteasome activity by controlling the expression of catalytic subunits, impacting longevity and protein homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jamal B. Williams, Qing Cao, Wei Wang, Young-Ho Lee, Luye Qin, Ping Zhong, Yong Ren, Kaijie Ma, Zhen Yan
Summary: The study by Williams et al demonstrates that targeting the aberrant histone modifying enzyme Smyd3 has the potential to rescue NMDAR and cognitive deficits in a mouse model of Alzheimer's disease, highlighting the potential of epigenetic treatment in neurodegenerative diseases.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Enrique Alfaro, Elena Diaz-Garcia, Sara Garcia-Tovar, Ester Zamarron, Alberto Mangas, Raul Galera, Eduardo Lopez-Collazo, Francisco Garcia-Rio, Carolina Cubillos-Zapata
Summary: This study suggests that hypoxia may induce the overexpression of proteasome genes in COVID-19 patients, which is associated with lymphocyte count reduction, increased inflammatory markers, and clinical complications.
Review
Medicine, Research & Experimental
Ivan Fernandez-Cruz, Enrique Reynaud
Summary: The ubiquitin-proteasome system plays a critical role in maintaining protein homeostasis, and dysregulation of this system has been linked to various neurodegenerative diseases. Aging is recognized as a major risk factor for neurodegenerative diseases, with alterations in the expression of 26S proteasome subunits potentially contributing to disease progression. Understanding the interactions between proteasome subunits and disease-associated proteins may provide insights into the mechanisms underlying neurodegenerative diseases.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Elena Della Morte, Stefania Niada, Chiara Giannasi, Luigi Zagra, Anna Teresa Brini
Summary: This study found that TNF-α can rapidly induce a decrease in Cx43 expression in articular chondrocytes, mainly through the proteasomal pathway. The proteasome inhibitor MG132 and the synthetic factor TGF-β 1 can reverse this decrease. These results suggest a potentially important role of Cx43 perturbation in joint inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Valentina Albanese, Chiara Ruzza, Erika Marzola, Tatiana Bernardi, Martina Fabbri, Anna Fantinati, Claudio Trapella, Rainer K. Reinscheid, Federica Ferrari, Chiara Sturaro, Girolamo Calo, Giorgio Amendola, Sandro Cosconati, Salvatore Pacifico, Remo Guerrini, Delia Preti
Summary: Neuropeptide S modulates neurobiological functions through interaction with its receptor, with NPSR antagonists showing potential for treating substance abuse disorders. Compound 16, a new NPSR antagonist, demonstrated significantly improved potency in vivo, making it a valuable tool for studying the translational potential of the NPSergic system. Molecular modeling investigation provided insights into structure-activity relationships and ligand/NPSR interactions.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Valentina Gentili, Giulia Turrin, Paolo Marchetti, Sabrina Rizzo, Giovanna Schiuma, Silvia Beltrami, Virginia Cristofori, Davide Illuminati, Greta Compagnin, Claudio Trapella, Roberta Rizzo, Daria Bortolotti, Anna Fantinati
Summary: Compounds synthesized by researchers showed significant antiviral activity in human cells, with 9e demonstrating a lasting inhibitory effect on viral replication for over 7 days, indicating support for the use of these amphipathic fusion inhibitors in treating HHV-6 infections.
BIOORGANIC CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Matteo Zurlo, Francesco Nicoli, Monica Borgatti, Alessia Finotti, Roberto Gambari
Summary: The COVID-19 pandemic has been a challenge for global health, emphasizing the need for effective vaccines. Recent studies have shown that patients with beta-thalassemia have a high mortality rate from COVID-19, likely due to their immune deficiencies. Immunosuppression may also impact the effectiveness of COVID-19 vaccines, suggesting the use of immunomodulatory molecules as a potential solution.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Chemistry, Organic
Davide Illuminati, Anna Fantinati, Tiziano De Ventura, Daniela Perrone, Chiara Sturaro, Valentina Albanese, Erika Marzola, Virginia Cristofori, Julie Oble, Giovanni Poli, Claudio Trapella
Summary: A small library of NH-Boc- or NH-Fmoc-protected L-phenylalanines carrying methyl groups at positions 2 and 6 and diverse functionalities at position 4 has been synthesized through a Pd-catalyzed directed C-H dimethylation. The electronic and steric properties of the resulting amino acid derivatives can be altered by appending a variety of electron-withdrawing, electron-donating, or bulky groups.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Anna Fantinati, Giampaolo Morciano, Giulia Turrin, Gaia Pedriali, Salvatore Pacifico, Delia Preti, Valentina Albanese, Davide Illuminati, Virginia Cristofori, Carlotta Giorgi, Elena Tremoli, Paolo Pinton, Claudio Trapella
Summary: Maintaining high percentage of living and functional cells is crucial for treating neurodegenerative disorders and cardiovascular diseases. Research on modulators of the permeability transition pore complex (PTPC) activity is still challenging and requires further investigation.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Organic
Mattia Ghirardello, Maira Costantini, Alessandra Vecchi, Salvatore Pacifico, Daniele Pazzi, Franca Castiglione, Andrea Mele, Alberto Marra
Summary: This study investigates the anion-cation interactions and solvation shell of three series of new ionic liquids (ILs), prepared from low-cost, unprotected carbohydrates, using diffusion NMR and heteronuclear Overhauser correlation maps (HOESY).
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Neurosciences
Sabrine Bilel, Joaquim Azevedo Neto, Raffaella Arfe, Micaela Tirri, Rosa Maria Gaudio, Anna Fantinati, Tatiana Bernardi, Federica Boccuto, Beatrice Marchetti, Giorgia Corli, Giovanni Serpelloni, Fabio De-Giorgio, Davide Malfacini, Claudio Trapella, Girolamo Calo', Matteo Marti
Summary: This study investigates the pharmacodynamic profiles of three fentanyl analogues and reveals their high potency and selectivity, significant effects on mechanical and thermal analgesia, as well as impairments on motor and cardiorespiratory parameters.
Article
Biochemistry & Molecular Biology
Micaela Tirri, Raffaella Arfe, Sabrine Bilel, Giorgia Corli, Beatrice Marchetti, Anna Fantinati, Fabrizio Vincenzi, Fabio De-Giorgio, Cristian Camuto, Monica Mazzarino, Mario Barbieri, Rosa Maria Gaudio, Katia Varani, Pier Andrea Borea, Francesco Botre, Matteo Marti
Summary: This study compared the pharmacodynamic activity of synthetic cannabinoids JWH-175 and JWH-018 in vitro and in vivo, and evaluated the metabolic profile of JWH-175. The results showed that JWH-175 is a less potent cannabinoid receptor agonist compared to JWH-018 and is rapidly converted to JWH-018 in vivo. This study provides important insights into the pharmacotoxicological profile of JWH-175 and emphasizes the importance of studying the in vivo metabolism of synthetic cannabinoids for clinical toxicology and forensic purposes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tiziano De Ventura, Mariasole Perrone, Sonia Missiroli, Paolo Pinton, Paolo Marchetti, Giovanni Strazzabosco, Giulia Turrin, Davide Illuminati, Virginia Cristofori, Anna Fantinati, Martina Fabbri, Carlotta Giorgi, Claudio Trapella, Vinicio Zanirato
Summary: A new chalconoid, velutone F, from the Millettia velutina plant, has shown potent effects as an NLRP3-inflammasome inhibitor; the search for new NLRP3 inhibitors is a current topic of interest in medicinal chemistry. Researchers have reported the synthesis of velutone F and unknown non-natural regioisomers using different synthetic strategies, providing a useful pathway for further studies on NLRP3-inhibitors in the flavonoid class.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nanoscience & Nanotechnology
Jennifer Gracie, Francesco Zamberlan, Iain B. Andrews, Brian O. Smith, William J. Peveler
Summary: This article introduces a colorimetric test to determine the age of whisky. By analyzing the formation of gold nanoparticles, the age, chemical composition, and flavor characteristics of whisky can be determined. This simple reduction assay could serve as a useful tool for identifying the aged character of whisky.
ACS APPLIED NANO MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Riccardo Barbari, Chiara Tupini, Elisa Durini, Eleonora Gallerani, Francesco Nicoli, Ilaria Lampronti, Anna Baldisserotto, Stefano Manfredini
Summary: A current research trend in the health field is to discover multifunctional compounds that can interact with multiple biological targets, simplifying multidrug therapies and improving patient compliance. This study synthesized new chemicals with a benzothiazole structure and tested them for antioxidant, UV-filtering, and antitumor activities. Compound BZTcin4 showed excellent activity and selectivity towards Colo-38, with good antioxidant capacity and broad-spectrum photoprotective profile.
Article
Geriatrics & Gerontology
Manuela Dominique Wennekes, Renske Eilers, Antonella Caputo, Amandine Gagneux-Brunon, Riccardo Gavioli, Francesco Nicoli, Zoltan Voko, Aura Timen
Summary: The increasing life expectancy has led to more cases of infectious diseases in older adults. Vaccines are available for various infections, but their acceptance is crucial for effectiveness. This study aimed to analyze the perceptions and decision-making behavior of older adults in different countries regarding vaccinations and their information needs.
Article
Immunology
Davide Proietto, Beatrice Dallan, Eleonora Gallerani, Valentina Albanese, Sian Llewellyn-Lacey, David A. Price, Victor Appay, Salvatore Pacifico, Antonella Caputo, Francesco Nicoli, Riccardo Gavioli
Summary: Age-related changes in the immune system affect the ability of elderly individuals to generate effective CD8(+) T cell responses against SARS-CoV-2. Elderly individuals show a deficit in priming naive precursors into effector CD8(+) T cells, resulting in reduced diversity and expression frequency of IFN-gamma in CD8(+) T cell responses. These findings have implications for developing strategies to protect the elderly against COVID-19.
Article
Chemistry, Medicinal
Valentina Albanese, Sonia Missiroli, Mariasole Perrone, Martina Fabbri, Caterina Boncompagni, Salvatore Pacifico, Tiziano De Ventura, Antonella Ciancetta, Giulio Dondio, Franz Kricek, Paolo Pinton, Remo Guerrini, Delia Preti, Carlotta Giorgi
Summary: A series of aryl sulfonamide derivatives (ASDs) were designed and synthesized to inhibit the activation of the NLRP3 inflammasome. Compounds 6c, 7n, and 10 specifically inhibited NLRP3 activation at nanomolar concentrations without affecting the activation of other inflammasomes. These compounds were also found to reduce IL-1 beta production in vivo and attenuate melanoma tumor growth. The findings suggest that these potent NLRP3 inflammasome inhibitors could be considered for future therapeutic approaches in NLRP3 inflammasome-driven cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Chemistry, Physical
Francesco Zamberlan