Article
Neurosciences
Francisco Q. Goncalves, Filipe C. Matheus, Henrique B. Silva, Joana I. Real, Daniel Rial, Ricardo J. Rodrigues, Jean-Pierre Oses, Antonio C. Silva, Nelio Goncalves, Rui D. Prediger, Angelo R. Tome, Rodrigo A. Cunha
Summary: The increased release of ATP and the subsequent formation of extracellular adenosine, which activates A(2A)R, play a key role in the abnormal synaptic plasticity associated with the onset of motor symptoms in Parkinson's disease.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Liliana Dias, Daniela Pochmann, Cristina Lemos, Henrique B. Silva, Joana I. Real, Francisco Q. . Goncalves, Daniel Rial, Nelio Goncalves, Ana Patricia Simoes, Samira G. Ferreira, Paula Agostinho, Rodrigo A. . Cunha, Angelo R. . Tome
Summary: Increased ATP release and its extracellular catabolism through CD73 lead to the overactivation of A2AR in brain disorders. Blocking A2AR can alleviate mood and memory dysfunction caused by repeated stress, but it is unclear whether increased ATP release coupled to CD73-mediated adenosine formation contributes to A2AR overactivation under repeated stress. In this study, rats subjected to repeated stress showed increased release of ATP and increased CD73 density in the brain, and inhibiting CD73 activity attenuated mood and memory dysfunction. These findings suggest that modulating ATP release and CD73 activity could be potential strategies to alleviate the negative effects of repeated stress.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Herbert Zimmermann
Summary: Geoffrey Burnstock is recognized for establishing a new field of intercellular communication through nucleotide signaling. Purinergic signaling involves intracellular storage, release, extracellular hydrolysis of nucleotides, and their effects on target tissues. Ectonucleotidases play key roles in inactivating nucleotides, generating active hydrolysis products, and facilitating nucleoside recycling.
PURINERGIC SIGNALLING
(2021)
Article
Physiology
Cesar Eduardo Jacintho Moritz, Franccesco Pinto Boeno, Alexandra Ferreira Vieira, Samuel Vargas Munhoz, Juliete Nathali Scholl, Amanda de Fraga Dias, Pauline Rafaela Pizzato, Fabricio Figueiro, Ana Maria Oliveira Battastini, Alvaro Reischak-Oliveira
Summary: The study found that moderate-intensity aerobic exercise can modify the activity of purinergic enzymes and nucleotide levels, which are related to inflammatory responses. This suggests a purinergic signaling pathway plays a role in inflammatory responses triggered by exercise.
EXPERIMENTAL PHYSIOLOGY
(2021)
Article
Neurosciences
Masayoshi Tanaka, Eiji Shigetomi, Bijay Parajuli, Hiroaki Nagatomo, Youichi Shinozaki, Yuri Hirayama, Kozo Saito, Yuto Kubota, Yosuke Danjo, Ji Hwan Lee, Sun Kwang Kim, Junichi Nabekura, Schuichi Koizumi
Summary: mGluR5 in astrocytes is regulated by ATP/adenosine signals, which helps control synapse remodeling and potentially contributes to disease pathogenesis.
Article
Hematology
Michael N. Sayegh, Kimberly A. Cooney, Woojin M. Han, Lanfang Wang, Frederick Strobel, Laura M. Hansen, Andres J. Garcia, Rebecca D. Levit
Summary: This study investigates the use of an enzyme-loaded synthetic hydrogel for local adenosine generation to improve perfusion and inhibit inflammation in peripheral arterial ischemia. Results show that the CD73 hydrogel effectively increases adenosine levels in vivo and improves limb perfusion in animal models, providing a new strategy for future disease treatment.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Alexei Verkhratsky
Summary: Purines and pyrimidines are essential molecules for genetic code and bioenergetics. Through evolution, purines have been associated with damage-related extracellular signaling, while plants have developed a sophisticated purinergic signaling system. In vertebrates, the purinergic signaling system operates universally without anatomical or functional segregation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Nicholas Dale
Summary: This review emphasizes the importance of real-time measurements of extracellular ATP and adenosine concentrations, provides additional mechanistic insights, and outlines current techniques available for spatially localized measurements. The examples of CO2 and nutrient sensing highlight the impact of direct real-time measurements, demonstrating the role of purinergic signaling in breathing control, weight regulation, and sleep-wake state. Additionally, the complex mechanisms of activity-dependent adenosine release in different brain regions are discussed, underscoring the potential of whole blood purine measurements in clinical practice.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Xue-qi Liu, Jun-jie Wang, Xue Wu, Zhen-ni Liu, Bao-ming Wu, Xiong-wen Lv
Summary: The aim of this study was to explore the fibrogenic effects of ATP-P1Rs axis and ATP-P2Rs axis on alcohol-related liver fibrosis (ALF). C57BL/6J CD73 knock out (KO) mice were used as the experimental model. The results showed that adenosine receptors were increased in ALF, and knocking out CD73 decreased adenosine receptors expression, increased ATP expression, and reduced fibrosis. This study suggests that adenosine plays a more important role in ALF and blocking the ATP-P1Rs axis could be a potential treatment for ALF.
Article
Biotechnology & Applied Microbiology
Tatsuya Nishiyama, Rio Hoshino, Kenji Ueda
Summary: In this study, two Streptomyces strains (NE5-10 and Y2F8-2) exhibiting 5'-inosine monophosphate (IMP)-dephosphorylating activity were obtained from soil isolates. The responsible enzyme was purified and the coding sequence was identified in the whole genome sequence of each strain. Phylogenetic analysis showed that the isolated Streptomyces enzymes represent a novel group of bacterial 5'-nucleotidases. Enzymatic characterization revealed differences in optimal temperature and pH, dependence on divalent cations, and substrate specificity between the two Streptomyces enzymes.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Mabrouka Salem, Joanna Lecka, Julie Pelletier, Danielle Gomes Marconato, Aline Dumas, Luc Vallieres, Gaetan Brochu, Bernard Robaye, Christian Jobin, Jean Sevigny
Summary: NTPDase8 plays a protective role in intestinal inflammation by limiting the activation of P2Y(6) receptors in colonic epithelial cells, providing a potential novel therapeutic strategy for inflammatory bowel disease. Interventions targeting P2Y(6) receptors may protect against inflammation in the colon.
Review
Immunology
Ines Sophie Schaedlich, Riekje Winzer, Joschi Stabernack, Eva Tolosa, Tim Magnus, Bjoern Rissiek
Summary: In ischemic stroke, disruption of energy supply leads to primary neuronal injury and secondary sterile inflammation. ATP released during brain ischemia triggers an inflammatory cascade by activating microglia and recruiting immune cells, while the CD39 and CD73 enzymes degrade ATP into adenosine to balance the inflammatory environment. Adenosine has neuroprotective effects through A(1) receptor-mediated inhibition of excitotoxicity and anti-inflammatory capacities via A(2A) receptor activation.
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Review
Cell Biology
Karel P. Alcedo, Jessica L. Bowser, Natasha T. Snider
Summary: Purinergic signaling is a fundamental mechanism used by all cells to control their internal activities and interact with the environment. CD73, a key component of the purinergic system, has been studied in cancer therapy, but recent research shows its complex role in cellular homeostasis, physiological adaptation, and disease development.
TRENDS IN CELL BIOLOGY
(2021)
Article
Immunology
Julia Leao Batista Simoes, Helena Fornari Basso, Greicy Cristine Kosvoski, Jullye Gavioli, Filomena Marafon, Charles Elias Assmann, Fabiano Barbosa Carvalho, Margarete Dulce Bagatini
Summary: COVID-19 is caused by a new member of the Coronaviridae family, the SARS-CoV-2 virus, which infects the respiratory tract by binding to ACE2 receptors. The infection triggers immune responses and cytokine storm, leading to severe respiratory symptoms and potential organ failure. Modulating purinergic receptors may offer a promising therapeutic approach to mitigate the severity of the disease.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Cell Biology
Michele Zanoni, Anna Pegoraro, Elena Adinolfi, Elena De Marchi
Summary: Resistance to therapy remains a critical obstacle in cancer treatment. Purinergic signaling plays a pivotal role in the regulation of cancer cell metabolism, inflammation, and development. Targeting purinergic signaling may have translational applications in combination with conventional anticancer interventions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Parasitology
Walmir da Silva, Isadora Cunha Ribeiro, Joice de Melo Agripino, Victor Hugo Ferraz da Silva, Luciana Angelo de Souza, Tatiana Aparecida Oliveira, Gustavo Costa Bressan, Raphael de Souza Vasconcellos, Carole Dumas, Julie Pelletier, Jean Sevigny, Barbara Papadopoulou, Juliana Lopes Rangel Fietto
Summary: Leishmania infantum can modulate the host immune response to its own favor. By overexpressing or abolishing the expression of LiNTPDase1 and LiNTPDase2, we found that they play important roles in parasite growth in culture and macrophage infection.
Article
Engineering, Biomedical
Liliana Ivet Sous Naasani, Luiza Pretto, Carla Zanatelli, Thais Casagrande Paim, Aline Francielle Damo Souza, Pablo Fagundes Pase, Marilda Da Cruz Fernandes, Jean Sevigny, Marcia Rosangela Wink
Summary: Therapies for deep burn injuries are challenging globally. Human amniotic membrane (hAM) has been explored by regenerative medicine as a biomaterial for wound healing. A decellularized hAM can act as a scaffold for mesenchymal stromal cells (MSCs) without losing their stemness potential, making it suitable for cell therapy. In this study, decellularized hAM was used in combination with adipose-derived MSCs for the treatment of second-degree burns. The results showed improved wound healing and reduced inflammation, indicating the potential of this low-cost and readily available dressing for burn treatments.
Article
Medicine, Research & Experimental
Amanda Roberta Revoredo Vicentino, Vanderlei da Silva Fraga-Junior, Matheus Palazzo, Natalia Recardo Amorim Tasmo, Danielle A. S. Rodrigues, Shana Priscila Coutinho Barroso, Samila Natiane Ferreira, Anna Cristina Neves-Borges, Diego Allonso, Marcelo Rosado Fantappie, Julio Scharfstein, Ana Carolina Oliveira, Rosane Vianna-Jorge, Andre Macedo Vale, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio, Claudio Canetti, Claudia Farias Benjamim
Summary: This study investigated the differences in serum levels of inflammatory mediators between patients with COVID-19 and healthy controls. The results showed that the levels of inflammatory mediators were higher in critically ill patients compared to the control group, and the levels of HMGB1 were associated with the risk of death. The authors suggest that serum levels of HMGB1 could be used as a biomarker for severe prognosis of COVID-19.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Chunyang Bi, Laura Schaekel, Salahuddin Mirza, Katharina Sylvester, Julie Pelletier, Sang -Yong Lee, Thanigaimalai Pillaiyar, Jean Sevigny, Christa E. Mueller
Summary: Ticlopidine is an antithrombotic prodrug that inhibits platelet function by covalently blocking the P2Y12 receptor on thrombocytes. It was found that Ticlopidine also inhibits CD39, an enzyme involved in ATP hydrolysis. In this study, a comprehensive analysis of Ticlopidine derivatives was conducted, leading to the discovery of benzotetrahydropyridines as a novel class of allosteric CD39 inhibitors.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hafiza Amna Younus, Muhammad Saeed, Abid Mahmood, Muhammad Siraj Khan Jadoon, Abdul Hameed, Asnuzilawati Asari, Habsah Mohamad, Julie Pelletier, Jean Sevigny, Jamshed Iqbal, Mariya al-Rashida
Summary: This study describes the synthesis of highly selective inhibitors for human intestinal alkaline phosphatase (h-IAP) and human tissue non-specific alkaline phosphatase (h-TNAP), and evaluates their inhibitory activities against other nucleotidases. These inhibitors hold therapeutic potential and contribute to our understanding of the selective activation and/or inhibition of nucleotidase enzymes in different cells and tissues.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Gohar Zaman, Saif Ullah, Muhammad Uzair, Sania Batool, Haseen Ahmad, Farman Ullah, Julia Pelletier, Jean Sevigny, Jamshed Iqbal, Abbas Hassan
Summary: In this study, various thieno[3,2-d]pyrimidine derivatives were synthesized by treating different secondary amines through aromatic nucleophilic substitution reaction (SNAr) followed by Suzuki reaction. The synthesized compounds were screened for their hydrolytic activity inhibition against h-NTPdase1, h-NTPdase2, h-NTPdase3, and h-NTPdase8. Compound N-benzyl-N-methyl-7-phenylthieno[3,2-d]pyrimidin-4-amine 3j selectively inhibited h-NTPdase1 activity with an IC50 value of 0.62 +/- 0.02 µM, while compound 4d was the most potent inhibitor of h-NTPdase2 with a sub-micromolar IC50 value of 0.33 +/- 0.09 µM. Similarly, compounds 4c and 3b were found to be selective inhibitors for isozymes h-NTPdase3 (IC50=0.13 +/- 0.06 µM) and h-NTPdase8 (IC50=0.32 +/- 0.10 µM), respectively. Molecular docking study revealed the interactions with important amino acid residues.
Article
Biochemistry & Molecular Biology
Bruna Bellaver, Guilherme Povala, Pamela C. L. Ferreira, Joao Pedro Ferrari-Souza, Douglas T. Leffa, Firoza Z. Lussier, Andrea L. Benedet, Nicholas J. Ashton, Gallen Triana-Baltzer, Hartmuth C. Kolb, Cecile Tissot, Joseph Therriault, Stijn Servaes, Jenna Stevenson, Nesrine Rahmouni, Oscar L. Lopez, Dana L. Tudorascu, Victor L. Villemagne, Milos D. Ikonomovic, Serge Gauthier, Eduardo R. Zimmer, Henrik Zetterberg, Kaj Blennow, Howard J. Aizenstein, William E. Klunk, Beth E. Snitz, Pauline Maki, Rebecca C. Thurston, Ann D. Cohen, Mary Ganguli, Thomas K. Karikari, Pedro Rosa-Neto, Tharick A. Pascoal
Summary: Cross-sectional and longitudinal analyses demonstrate that tau tangles accumulate in preclinical Alzheimer's disease only in individuals positive for astrocyte reactivity biomarker. A significant percentage of cognitively unimpaired individuals positive for amyloid-beta do not develop detectable downstream tau pathology, but the presence of reactive astrocytes modulates the association between amyloid-beta and tau phosphorylation. These findings suggest that astrocyte reactivity plays a crucial role in linking amyloid-beta with initial tau pathology, with implications for the biological definition of preclinical Alzheimer's disease and selection of individuals for clinical trials.
Article
Clinical Neurology
Pamela C. L. Ferreira, Joao Pedro Ferrari-Souza, Cecile Tissot, Bruna Bellaver, Douglas T. Leffa, Firoza Lussier, Guilherme Povala, Joseph Therriault, Andrea L. Benedet, Nicholas J. Ashton, Ann D. Cohen, Oscar L. Lopez, Dana L. Tudorascu, William E. Klunk, Jean-Paul Soucy, Serge Gauthier, Victor Villemagne, Henrik Zetterberg, Kaj Blennow, Pedro Rosa-Neto, Eduardo R. Zimmer, Thomas K. Karikari, Tharick A. Pascoal
Summary: This study tested the effectiveness of longitudinal changes in plasma phosphorylated tau 181 (p-tau181) and neurofilament light chain (NfL) as surrogate markers for clinical trials in cognitively unimpaired populations. The findings suggest that monitoring plasma markers in such individuals is a viable approach for large-scale interventions.
Article
Cell Biology
Fabricia L. Fontes-Dantas, Gabriel G. Fernandes, Elisa G. Gutman, Emanuelle V. De Lima, Leticia S. Antonio, Mariana B. Hammerle, Hannah P. Mota-Araujo, Lilian C. Colodeti, Suzana M. B. Araujo, Gabrielle M. Froz, Talita N. da Silva, Larissa A. Duarte, Andreza L. Salvio, Karina L. Pires, Luciane A. A. Leon, Claudia Cristina F. Vasconcelos, Luciana Romao, Luiz Eduardo B. Savio, Jerson L. Silva, Robson da Costa, Julia R. Clarke, Andrea T. Da Poian, Soniza V. Alves-Leon, Giselle F. Passos, Claudia P. Figueiredo
Summary: Cognitive dysfunction in post-COVID-19 syndrome may be caused by the release of SARS-CoV-2 Spike protein, which can lead to neuroinflammation, synapse elimination, and memory dysfunction mediated by Toll-like receptor 4 (TLR4) signaling. Infusing Spike protein into the brains of mice reproduced cognitive impairment similar to post-COVID-19 syndrome. In a group of 86 mild COVID-19 patients, a specific TLR4 genotype was associated with poor cognitive outcome. These findings highlight TLR4 as a key target for investigating long-term cognitive dysfunction after COVID-19 infection.
Article
Pharmacology & Pharmacy
Vinicius Santos Alves, Joyce Pereira da Silva, Fabiana Cristina Rodrigues, Suzana Maria Bernardino Araujo, Andre Luiz Gouvea, Raissa Leite-Aguiar, Stephanie Alexia Cristina Silva Santos, Milla Souza Pessoa da Silva, Fernanda Silva Ferreira, Eduardo Peil Marques, Beatriz Amanda Barbosa Rangel dos Passos, Tatiana Maron-Gutierrez, Eleonora Kurtenbach, Robson da Costa, Claudia Pinto Figueiredo, Angela T. S. Wyse, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio
Summary: Sepsis is a severe and potentially fatal condition caused by multiple factors, which can lead to a high risk of death. Sepsis-associated encephalopathy is a condition where the intense inflammatory response has detrimental effects on the brain. The activation of the P2X7 receptor, which is abundantly expressed in the brain, plays a role in chronic neurodegenerative and neuroinflammatory diseases, but its function in long-term neurological impairment caused by sepsis is still unclear.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Immunology
Cassio Luiz Coutinho Almeida-da-Silva, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva, David M. Ojcius
Summary: The innate immune system in vertebrates and invertebrates relies on conserved receptors and ligands, and pathways to initiate a rapid response against microbial infections and other sources of stress and danger. Research on NOD-like receptors (NLRs) has advanced in the past two decades, providing insight into the ligands and conditions that activate NLRs, as well as the outcomes of NLR activation in cells and animals. NLRs play crucial roles in diverse functions, such as transcription of MHC molecules and initiation of inflammation, and their activation can be direct or indirect depending on the ligands involved. Future discoveries will contribute to a better understanding of the molecular details and physiological consequences of NLR activation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Vinicius Santos Alves, Stephanie Alexia Cristina Silva Santos, Raissa Leite-Aguiar, Elaine Paiva-Pereira, Renata Rodrigues dos Reis, Mariana L. Calazans, Gabriel Gripp Fernandes, Leticia Silva Antonio, Emanuelle V. de Lima, Eleonora Kurtenbach, Jerson Lima Silva, Fabricia Lima Fontes-Dantas, Giselle Fazzioni Passos, Claudia Pinto Figueiredo, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio
Summary: Despite the unclear mechanism, the Spike protein of SARS-CoV-2 can affect microglial purinergic signaling and may play a role in the neuropathology of COVID-19. Evidence suggests that the Spike protein can activate pattern recognition receptors and cause neuroinflammation, leading to long-term sequelae of the disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julie Favre, Charlotte Roy, Anne-Laure Guihot, Annick Drouin, Manon Laprise, Marc-Antoine Gillis, Simon C. Robson, Eric Thorin, Jean Sevigny, Daniel Henrion, Gilles Kauffenstein
Summary: NTPDase1/CD39 plays a thrombo-immunoregulatory role by controlling endothelial P2 receptor activation. The study highlights the key regulatory function of CD39 in short-term and long-term arterial diameter adaptation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Liliana Ivet Sous Naasani, Jessica Gonsalves Azevedoa, Jean Sevigny, Tiago Franco de Oliveira, Silvya Stuchi Maria-Engler, Marcia Rosangela Wink
Summary: This study reveals the expression and function of ectonucleotidases in human epidermal melanocytes, suggesting their involvement in regulating nucleotide levels in the skin microenvironment.
BIOCHEMISTRY AND CELL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Muhammad Siraj Khan Jadoon, Julie Pelletier, Jean Sevigny, Jamshed Iqbal
Summary: This article investigates the potential of substituted indole acetic acid sulfonate derivatives as ectonucleotidase inhibitors, showing that these compounds can inhibit tumor development and immune evasion, and have selectivity and potency.
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.