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Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases

Grant number: 18/07366-4
Support type:Research Projects - Thematic Grants
Duration: April 01, 2019 - March 31, 2024
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Alexander Henning Ulrich
Grantee:Alexander Henning Ulrich
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
( Atuais )
Luiz Roberto Giorgetti de Britto
Pesquisadores principais:
( Anteriores )
Marimélia Aparecida Porcionatto
Assoc. researchers:Beatriz de Oliveira Monteiro ; Claudiana Lameu ; Cristiane Otero Reis Salum ; João Bosco Pesquero ; Luiz Henrique Catalani ; Marimélia Aparecida Porcionatto ; Mayana Zatz ; Roberto de Pasquale ; Roberto Kopke Salinas ; Silvana Chiavegatto
Associated scholarship(s):22/01304-2 - In vitro studies of the role of P2X4 receptors on inflammatory processes involved in Parkinsons Disease, BP.MS
21/01478-8 - Molecular effects of pharmacological modulation of P2Y6 receptors in an in vitro model for the study of Alzheimer's Disease, BP.MS
21/00060-0 - Role of P2Y14 receptor modulation in the hippocampal neuroinflammatory responses in in vitro and in vivo models of Alzheimer's Disease, BP.PD
+ associated scholarships 21/05279-0 - The role of purinergic receptors and Huntingtin in gastrulation, BP.TT
21/04174-0 - Study of the bipolar disorder and Alzheimer's disease comorbidity using 3D cultures of decellularized brain extracellular matrix, BP.TT
20/10725-6 - Evaluation of purinergic receptors in the comorbidity of bipolar disorder and Alzheimer's Disease, BP.DD
20/07609-4 - Study of the neuroregeneration process triggered by bradykinin in the animal model of Parkinson's Disease, BP.IC
19/24553-5 - The role of P2Y1 receptor in Parkinsons Disease, BP.DR
19/26852-0 - Study of purinergic receptors antagonism in the inflammatory process and microglial cells activation using in vitro and in vivo models of Parkinsons Disease, BP.PD
18/17504-5 - Behavioral and molecular effects of pharmacological modulation of the P2Y2 receptors in an animal model of Alzheimer's Disease, BP.PD
19/03494-0 - Silencing of B1R and B2R kinin receptors in the BV-2 microglial cell line as a model of neuroinflammation response, BP.IC
15/15826-7 - Collagen hydrogel modified by bi-functional recombinant protein for transplantation of neural stem cells for the treatment of neurodegenerative disorder, BP.PD
15/19478-3 - Role of kinin-B2 receptor in pathogenesis and progression of familial Alzheimer's Disease: from neurogenesis and immune response to cognition, BP.PD
15/13345-1 - Huntington's disease: Huntingtin roles during cell fate decision, BP.PD - associated scholarships

Abstract

The biological process of neurogenesis that consists of differentiation of neural stem cells (NSC) into neurons, occurs both in embryonic and adult phases. Therefore, NSC are being proposed as interesting tools for nervous system tissue regeneration and restoration of physiological conditions, as well as models for elucidation of pathophysiological development of neurological diseases. Previous studies of our laboratory showed several signalling pathways involved in NSC development, especially through purinergic and kininergic receptors, whose modulation is essential in neural phenotype determination. Besides participating in adult brain neurotransmition in health conditions, their modulation reverted pathologic scenarios in animal and in vitro models of Parkinson's and Alzheimer's Disease. Taking into account these findings of our group, we proposed here a more profound investigation regarding mechanisms underlying in these effects, elucidating how purinergic and kininergic systems are involved and potential therapeutic targets for neurologic pathologies, especially associated with neurodegeneration/ regeneration and inflammatory process. Thus, the neurogenic, neuroprotective and immunomodulatory effects of purinergic and kininergic signalling will be studied in Parkinson's, Alzheimer's and Huntington's diseases and in bipolar disorder. Moreover, new tools based on nanotechnology, as biopolymers conjugated to bradikinin, will be used in NSC transplantation improvement as therapeutic alternative in animal models. (AU)

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Scientific publications (33)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PILLAT, MICHELI MAINARDI; OLIVEIRA-GIACOMELLI, AGATHA; DAS NEVES OLIVEIRA, MONA; ANDREJEW, ROBERTA; TURRINI, NATALIA; BARANOVA, JULIANA; LAH TURNSEK, TAMARA; ULRICH, HENNING. Mesenchymal stem cell-glioblastoma interactions mediated via kinin receptors unveiled by cytometry. Cytometry Part A, v. 99, n. 2, SI, . (18/07366-4, 20/10725-6, 12/50880-4, 19/24553-5, 19/26852-0)
REICHERT, KARINE P.; PILLAT, MICHELI M.; SCHETINGER, MARIA ROSA C.; BOTTARI, NATHIELI B.; PALMA, V, TAIS; ASSMANN, CHARLES E.; GUTIERRES, JESSIE M.; ULRICH, HENNING; ANDRADE, CINTHIA M.; EXLEY, CHRISTOPHER; et al. Aluminum-induced alterations of purinergic signalling in embryonic neural progenitor cells. Chemosphere, v. 251, . (18/07366-4, 15/19478-3)
OLIVEIRA-GIACOMELLI, AGATHA; PETIZ, LYVIA LINTZMAIER; ANDREJEW, ROBERTA; TURRINI, NATALIA; SILVA, JEAN BEZERRA; SACK, ULRICH; ULRICH, HENNING. Role of P2X7 Receptors in Immune Responses During Neurodegeneration. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 15, . (18/08426-0, 19/24553-5, 18/07366-4, 19/26852-0, 20/10725-6)
DO NASCIMENTO, RAVENA PEREIRA; DOS SANTOS, BALBINO LINO; AMPARO, JESSIKA ALVES OLIVEIRA; SOARES, JANAINA RIBEIRO PEREIRA; DA SILVA, KARINA COSTA; SANTANA, MONIQUE REIS; ALMEIDA, AUREA MARIA ALVES NUNES; DA SILVA, VICTOR DIOGENES AMARAL; COSTA, MARIA DE FATIMA DIAS; ULRICH, HENNING; et al. euroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastom. PHARMACEUTICS, v. 14, n. 1, . (18/07366-4)
ANDREJEW, ROBERTA; OLIVEIRA-GIACOMELLI, AGATHA; RIBEIRO, DEIDIANE ELISA; GLASER, TALITA; ARNAUD-SAMPAIO, VANESSA FERNANDES; LAMEU, CLAUDIANA; ULRICH, HENNING. The P2X7 Receptor: Central Hub of Brain Diseases. FRONTIERS IN MOLECULAR NEUROSCIENCE, v. 13, . (15/13345-1, 18/17504-5, 19/24553-5, 15/19128-2, 18/07366-4)
PILLAT, MICHELI MAINARDI; KRUGER, ARNE; FERREIRA GUIMARAES, LARA MENDES; LAMEU, CLAUDIANA; DE SOUZA, EDMARCIA ELISA; WRENGER, CARSTEN; ULRICH, HENNING. Insights in Chloroquine Action: Perspectives and Implications in Malaria andCOVID-19. Cytometry Part A, v. 97, n. 9, . (18/08820-0, 15/26722-8, 18/07366-4, 15/19128-2)
VIVIANI, LUCAS G.; PICCIRILLO, ERIKA; ULRICH, HENNING; AMARAL, ANTONIA T-DO. Virtual Screening Approach for the Identification of Hydroxamic Acids as Novel Human Ecto-5 `-Nucleotidase Inhibitors. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 60, n. 2, p. 621-630, . (18/07366-4, 18/24678-0, 13/07937-8, 18/06381-0, 14/07248-0, 12/06633-2, 12/50880-4)
OLIVEIRA-GIACOMELLI, AGATHA; ALBINO, CAROLINA M.; NOBREGA DE SOUZA, HELLIO DANNY; CORREA-VELLOSO, JULIANA; DE JESUS SANTOS, ANA PAULA; BARANOVA, JULIANA; ULRICH, HENNING. P2Y6 and P2X7 Receptor Antagonism Exerts Neuroprotective/ Neuroregenerative Effects in an Animal Model of Parkinson's Disease. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 13, . (12/50880-4, 18/07366-4, 17/24400-9)
ARNAUD-SAMPAIO, VANESSA FERNANDES; ALVES RABELO, IZADORA LORRANY; ULRICH, HENNING; LAMEU, CLAUDIANA. The P2X7 Receptor in the Maintenance of Cancer Stem Cells, Chemoresistance and Metastasis. STEM CELL REVIEWS AND REPORTS, v. 16, n. 2, p. 288-300, . (15/19128-2, 18/07366-4, 17/06132-7)
CORREA-VELLOSO, JULIANA C.; BARTLETT, PAULA J.; BRUMER, ROBERT; GASPERS, LAWRENCE D.; ULRICH, HENNING; THOMAS, ANDREW P.. Receptor-specific Ca2+ oscillation patterns mediated by differential regulation of P2Y purinergic receptors in rat hepatocytes. ISCIENCE, v. 24, n. 10, . (18/07366-4)
KRUGER, ARNE; DE JESUS SANTOS, ANA PAULA; DE SA, VANESSA; ULRICH, HENNING; WRENGER, CARSTEN. Aptamer Applications in Emerging Viral Diseases. PHARMACEUTICALS, v. 14, n. 7, . (18/07366-4, 15/26722-8, 17/03966-4, 15/26642-4)
ARNAUD-SAMPAIO, VANESSA F.; RABELO, IZADORA L. A.; BENTO, CAROLINA A.; GLASER, TALITA; BEZERRA, JEAN; COUTINHO-SILVA, ROBSON; ULRICH, HENNING; LAMEU, CLAUDIANA. Using Cytometry for Investigation of Purinergic Signaling in Tumor-Associated Macrophages. Cytometry Part A, v. 97, n. 11, . (17/06132-7, 15/13345-1, 18/07366-4, 18/14993-5, 15/19128-2)
TOMCZYK, MARTA; GLASER, TALITA; SLOMINSKA, EWA M.; ULRICH, HENNING; SMOLENSKI, RYSZARD T.. Purine Nucleotides Metabolism and Signaling in Huntington's Disease: Search for a Target for Novel Therapies. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 12, . (18/07366-4)
RATAJCZAK, MARIUSZ Z.; ADAMIAK, MATEUSZ; BUJKO, KAMILA; THAPA, ARJUN; PENSATO, VALENTINA; KUCIA, MAGDA; RATAJCZAK, JANINA; ULRICH, HENNING. Innate immunity orchestrates the mobilization and homing of hematopoietic stem/progenitor cells by engaging purinergic signaling-an update. PURINERGIC SIGNALLING, . (18/07366-4)
PALMA, TAIS VIDAL; LENZ, LUANA SUELING; BOTTARI, NATHIELE BIANCHIN; PEREIRA, ALINE; SCHETINGER, MARIA ROSA CHITOLINA; MORSCH, VERA MARIA; ULRICH, HENNING; PILLAT, MICHELI MAINARDI; DE ANDRADE, CINTHIA MELAZZO. Berberine induces apoptosis in glioblastoma multiforme U87MG cells via oxidative stress and independent of AMPK activity. MOLECULAR BIOLOGY REPORTS, v. 47, n. 6, . (18/07366-4)
GLASER, TALITA; SHIMOJO, HIROMI; RIBEIRO, DEIDIANE ELISA; MARTINS, PATRICIA PEREIRA LOPES; BECO, RENATA PEREIRA; KOSINSKI, MICHAL; SAMPAIO, VANESSA FERNANDES ARNAUD; CORREA-VELLOSO, JULIANA; OLIVEIRA-GIACOMELLI, AGATHA; LAMEU, CLAUDIANA; et al. ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington's disease: a novel approach for cell clock research. MOLECULAR PSYCHIATRY, v. 26, n. 6, p. 2633-2650, . (18/07366-4, 15/13345-1, 12/50880-4)
FERNANDES FERREIRA, ANA FLAVIA; SINGULANI, MONIQUE PATRICIO; ULRICH, HENNING; FENG, ZHONG-PING; SUN, HONG-SHUO; BRITTO, LUIZ ROBERTO. Inhibition of TRPM2 by AG490 Is Neuroprotective in a Parkinson's Disease Animal Model. Molecular Neurobiology, . (18/07366-4, 20/02109-3)
CAMPOS, HENRIQUE C.; RIBEIRO, DEIDIANE ELISA; HASHIGUCHI, DEBORA; HUKUDA, DEBORAH Y.; GIMENES, CHRISTIANE; ROMARIZ, SIMONE A. A.; YE, QING; TANG, YONG; ULRICH, HENNING; LONGO, BEATRIZ MONTEIRO. Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer's Disease. STEM CELL REVIEWS AND REPORTS, . (17/12412-2, 18/07366-4)
WANG, TAO; ULRICH, HENNING; SEMYANOV, ALEXEY; ILLES, PETER; TANG, YONG. Optical control of purinergic signaling. PURINERGIC SIGNALLING, v. 17, n. 3, p. 385-392, . (18/07366-4)
RABELO, IZADORA LORRANY ALVES; ARNAUD-SAMPAIO, VANESSA FERNANDES; ADINOLFI, ELENA; ULRICH, HENNING; LAMEU, CLAUDIANA. Cancer Metabostemness and Metabolic Reprogramming via P2X7 Receptor. CELLS, v. 10, n. 7, . (17/06132-7, 15/19128-2, 18/07366-4)
HUANG, ZHAO; XIE, NA; ILLES, PETER; DI VIRGILIO, FRANCESCO; ULRICH, HENNING; SEMYANOV, ALEXEY; VERKHRATSKY, ALEXEI; SPERLAGH, BEATA; YU, SHU-GUANG; HUANG, CANHUA; et al. From purines to purinergic signalling: molecular functions and human diseases. SIGNAL TRANSDUCTION AND TARGETED THERAPY, v. 6, n. 1, . (18/07366-4)
MIRANDA, ALVARO; MONTIEL, ENRIQUE; ULRICH, HENNING; PAZ, CRISTIAN. Selective Secretase Targeting for Alzheimer's Disease Therapy. JOURNAL OF ALZHEIMER'S DISEASE, v. 81, n. 1, p. 1-17, . (18/07366-4)
SANTOS, ANDERSON K.; GOMES, KATIA N.; PARREIRA, RICARDO C.; SCALZO, SERGIO; PINTO, MAURO C. X.; SANTIAGO, HELTON C.; BIRBRAIR, ALEXANDER; SACK, ULRICH; ULRICH, HENNING; RESENDE, RODRIGO R.. Mouse Neural Stem Cell Differentiation and Human Adipose Mesenchymal Stem Cell Transdifferentiation Into Neuron-and Oligodendrocyte-like Cells With Myelination Potential. STEM CELL REVIEWS AND REPORTS, . (18/07366-4)
PALMA, TAIS VIDAL; BIANCHIN, NATHIELE BOTARI; DE OLIVEIRA, JULIANA SORRAILA; ASSMANN, CHARLES ELIAS; DAS NEVES OLIVEIRA, MONA; SCHETINGER, MARIA ROSA CHITOLINA; MORSCH, VERA MARIA; ULRICH, HENNING; PILLAT, MICHELI MAINARDI; DE ANDRADE, CINTHIA MELAZZO. erberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cell. MOLECULAR BIOLOGY REPORTS, v. 49, n. 3, . (18/07366-4)
ADAMIAK, MATEUSZ; BUJKO, KAMILA; THAPA, ARJUN; PENSATO, VALENTINA; BRZEZNIAKIEWICZ-JANUS, KATARZYNA; RATAJCZAK, JANINA; DAVIES, DARYL L.; ULRICH, HENNING; KUCIA, MAGDA; RATAJCZAK, MARIUSZ Z.. The P2X4 purinergic receptor has emerged as a potent regulator of hematopoietic stem/progenitor cell mobilization and homing-a novel view of P2X4 and P2X7 receptor interaction in orchestrating stem cell trafficking. LEUKEMIA, v. 36, n. 1, . (18/07366-4)
CAO, XIN; YIN, HAI-YAN; ULRICH, HENNING; SEMYANOV, ALEXEY; TANG, YONG. A Neural Circuit for Gut-Induced Sugar Preference. NEUROSCIENCE BULLETIN, v. 37, n. 5, p. 754-756, . (18/07366-4)
MACHADO, RAFAEL R. G.; GLASER, TALITA; ARAUJO, DANIELLE B.; PETIZ, LYVIA LINTZMAIER; OLIVEIRA, DANIELLE B. L.; DURIGON, GIULIANA S.; LEAL, ALESSANDRA L.; PINHO, JOAO RENATO R.; FERREIRA, LUIS C. S.; ULRICH, HENNING; et al. Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells. ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, v. 4, n. 5, p. 1514-1527, . (20/06409-1, 19/00195-2, 18/07366-4, 17/24769-2, 16/20045-7, 20/04680-0)
PETIZ, LYVIA LINTZMAIER; GLASER, TALITA; SCHARFSTEIN, JULIO; RATAJCZAK, MARIUSZ Z.; ULRICH, HENNING. P2Y14 Receptor as a Target for Neutrophilia Attenuation in Severe COVID-19 Cases: From Hematopoietic Stem Cell Recruitment and Chemotaxis to Thrombo-inflammation. STEM CELL REVIEWS AND REPORTS, v. 17, n. 1, SI, . (18/07366-4, 15/13345-1)
TROMBETTA-LIMA, MARINA; ASSIS-RIBAS, THAIS; CINTRA, RICARDO C.; CAMPEIRO, JOANA D.; GUERREIRO, JULIANO R.; WINNISCHOFER, SHEILA M. B.; NASCIMENTO, ISIS C. C.; ULRICH, HENNING; HAYASHI, MIRIAN A. F.; SOGAYAR, MARI C.. Impact of Reck expression and promoter activity in neuronal in vitro differentiation. MOLECULAR BIOLOGY REPORTS, v. 48, n. 2, . (18/20014-0, 16/05311-2, 18/07366-4, 14/50891-1, 19/13112-8, 15/26328-8, 16/18277-7, 12/50880-4, 17/02413-1)
GLASER, TALITA; ANDREJEW, ROBERTA; OLIVEIRA-GIACOMELLI, AGATHA; RIBEIRO, DEIDIANE ELISA; MARQUES, LUCAS BONFIM; YE, QING; REN, WEN-JING; SEMYANOV, ALEXEY; ILLES, PETER; TANG, YONG; et al. Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington's and Parkinson's Disease. NEUROSCIENCE BULLETIN, v. 36, n. 11, SI, p. 1299-1314, . (15/13345-1, 19/24553-5, 18/17504-5, 19/26852-0, 18/07366-4)
RIBEIRO, DEIDIANE ELISA; OLIVEIRA-GIACOMELLI, AGATHA; GLASER, TALITA; ARNAUD-SAMPAIO, VANESSA F.; ANDREJEW, ROBERTA; DIECKMANN, LUIZ; BARANOVA, JULIANA; LAMEU, CLAUDIANA; RATAJCZAK, MARIUSZ Z.; ULRICH, HENNING. Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology. MOLECULAR PSYCHIATRY, v. 26, n. 4, . (15/13345-1, 19/24553-5, 18/17504-5, 15/19128-2, 19/26852-0, 18/07366-4)
TRUJILLO, CLEBER A.; ADAMS, JASON W.; NEGRAES, PRISCILLA D.; CARROMEU, CASSIANO; TEJWANI, LEON; ACAB, ALLAN; TSUDA, BEN; THOMAS, CHARLES A.; SODHI, NEHA; FICHTER, KATHERINE M.; et al. Pharmacological reversal of synaptic and network pathology in human MECP2-KO neurons and cortical organoids. EMBO MOLECULAR MEDICINE, v. 13, n. 1, . (18/07366-4)
BOTTARI, NATHIELI B.; REICHERT, KARINE PAULA; FRACASSO, MATEUS; DUTRA, ANIELEN; ASSMANN, CHARLES ELIAS; ULRICH, HENNING; CHITOLINA SCHETINGER, MARIA ROSA; MORSCH, VERA M.; DA SILVA, ALEKSANDRO SCHAFER. Neuroprotective role of resveratrol mediated by purinergic signalling in cerebral cortex of mice infected byToxoplasma gondii. Parasitology Research, v. 119, n. 9, . (18/07366-4)

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