Title: Novel insights into P2X3 and A3 receptor contribution to pain states
Chairs: Peter Illes (Leipzig, Germany) / Antonio R. Artalejo (Madrid, Spain)
- Antonio R. Artalejo (Universidad Complutense de Madrid, Spain) Overexpression of P2X3 and P2X7 receptors and TRPV1 channels in adrenomedullary chromaffin cells in a rat model of neuropathic pain
- Patrizia Rubini (Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Leipzig, Germany) The ASIC3/P2X3 cognate receptor senses acidic and purinergic pain in a novel manner
- Elisabetta Coppi (Department of Neuroscience, University of Florence, Italy). Molecular mechanisms for A3 adenosine receptor mediated pain control: an in vitro study on dorsal root ganglion neuron excitability
- Livio Luongo (Department of Experimental Medicine, Division of Pharmacology, University of Campania “L. Vanvitelli”, Naples, Italy) Targeting adenosine receptors to treat neuropathic pain
Content: Purines signal sensory information involved in nociception. Although a variety of P1 and P2 receptors are known to mediate nociceptive transmission, recent findings on novel P2X3 receptor supramolecular complexes and locations as well as on the role adenosine A3 receptors in pain pathways are opening new avenues for the development of more effective and safer analgesics.
Title: New insights into purinergic signaling
Chairs: Esmerilda G. Delicado (Madrid, Spain) / Jürgen Schrader (Düsseldorf, Germany)
- Jürgen Schrader (IMC/HH University, Dusseldorf, Germany) CD73-derived adenosine in inflammation: mechanisms and relevance
- Lisardo Boscá (IIBM/CSIC, Madrid, Spain) Crossroad between bioactive lipids and purinergic signalling in macrophages
- Alejandro Sánchez Melgar (CRIB, UCLM, Ciudad Real, Spain) Adenosine receptors as a primary target for resveratrol: From antitumoral to neuroprotection action
- Esmerilda G Delicado (BD/UCM, Madrid, Spain) Cross-talk between P2 receptors and tyrosine kinase receptors in cerebellar astrocytes
- Juan Vicente Esplugues (FDM, UV, Valencia, Spain) Drug-induced cardiovascular toxicity mediated by P2X7 receptors : the example of Abacavir
Content: The symposium shows some examples of the implications of different components of purinergic signaling, ectoenzymes, nucleotide and adenosine receptors, in inflammation, neuroprotection and virus infection. It emphasizes the complexity of purinergic signaling and the multiple targets that could be considered for clinical interventions.
Title: Purinergic receptors as future targets in Alzheimer’s Disease?
Chairs: David Blum (Lille, France) / Annett Halle (Bonn, Germany)
- Lauriane Ulmann (CNRS, Montpellier, France) Involvement of purinergic P2X4 receptors in Alzheimer disease
- Nicole Reichenbach (DZNE, Bonn, Germany) Role of astroglial purinergic transmission in Alzheimer´s disease
- Joao Pedro Lopes (University of Coimbra, Coimbra, Portugal) ATP-derived adenosine controls synaptic and memory dysfunction in β-amyloid models of Alzheimer’s disease
- Annett Halle (DZNE, Bonn, Germany) Purinergic signaling shapes microglial functions in Alzheimer’s disease
Content: Alzheimer’s Disease is a major health concern with no treatment available to significantly slow down or halt cognitive symptoms. Facing approaches which target neuropathological lesions and that have not proven efficiency yet, it is mandatory to develop alternative strategies. Purine homeostasis is disrupted in Alzheimer’s Disease involving immune and plasticity dysfunctions which favor the development of cognitive deficits. In the present symposium, speakers will give new insights into the role of purinergic signaling in thepathophysiological development of Alzheimer’s Disease and discuss the therapeutic perspectives.
Title: How purinergic signaling influences the activity of human mesenchymal stromal/stem cells
Chairs: Renata Ciccarelli (Chieti, Italy) / Lin-Hua Jiang (Leeds, UK)
- Renata Ciccarelli (University of Chieti-Pescara, Chieti, Italy) Influence of different purine receptors on the differentiation potential or malignancy of normal or cancerous mesenchymal stem cells, respectively
- Edda Tobiasch (Bonn-Rhine-Sieg University of Applied Sciences, Reinbach, Germany) Enhanced osteogenesis and angiogenesis for putative bone grafts by activating purinergic receptor signaling during mesenchymal stem cell differentiation
- Lin-Hua Jiang (School of Biomedical Sciences, University of Leeds, Leeds, UK) ATP-induced calcium signaling in mesenchymal stem cell functions
- Magdalen Wujak (N. Copernicus University, Torun, Poland) Emerging role of nucleotide-metabolizing enzymes in regulation of mesenchymal stem cell fate
Content: The aim of this symposium is to give an overview of recent advances on the influence of purines on the activity/function of mesenchymal stromal/stem cells (MSCs).
These cells, which can be isolated from different human adult tissues (i.e. bone marrow, adipose or dental tissues) and embryonic annexes (umbilical cord, placenta) or fluids (amniotic liquid) are today actively studied given the great differentiation potential of these cells, which represent a possible new therapeutic tool in regenerative medicine. Stem cells are also present in tumors as a restrict population generally provided with a great invasiveness and resistance to radio- and chemo-therapy. Thus, considering that purines are ancestral molecules present in and released from virtually all cell types, including normal or tumor MSCs, there is a growing interest to explore which purines are mostly present in the extracellular environment (due to the extensive metabolism of released nucleotides by ecto-enzymes) and how endogenous or exogenous purines can influence MSC potentialities by interacting with their own receptors as signaling molecules. Accordingly, this symposium will examine different aspects of the purine involvement in the modulation of physiological/pathological MSC functions and differentiation ability of these cells, including the control of intracellular calcium levels, which play a crucial role also in MSC homeostasis.
Title: Membrane transporters and purinergic signalling
Chairs: Marçal Pastor-Anglada (Barcelona, Spain) / Beatriz Lopez-Corcuera (Madrid, Spain)
- Beatriz Lopez-Corcuera (Madrid, Spain) Modulation of neuronal glycine transport by P2Y and P2X receptors
- Sandra Pérez-Torras (Barcelona, Spain) Role of Concentrative Nucleoside Transporters (CNT) in adenosine transport and metabolism
- Felipe Ortega (Madrid, Spain) Live imaging and single cell tracking reveals cell dynamics from early cerebellar neural stem cells. Role of VNUT in their lineage progression
Young scientist speakers
Content: Membrane purine transporters contribute to the modulation of nucleotide and adenosine tones. Moreover, the biological function of selected membrane transporters, including adenosine and neurotransmitter transporters, is also regulated by P1 and P2 receptors. These concepts will be illustrated and discussed in this symposium.
Title: New genetic tools for understanding cell-specific purinoceptor function in health and diseases
Chairs: Annette Nicke (Munich, Germany)
- Eric Boué-Grabot (Bordeaux, France) Increased surface P2X4 receptor expression leads to synaptic plasticity and learning deficits in non-internalized P2X4mCherryIN knockin mice
- David Blum (Lille, France) A new conditional model to study adenosine A2AR dysfunction in Alzheimer’s Disease
- Robin Kopp (Frankfurt, Germany) In-situ cross-linking of P2X7 complexes to identify protein-protein interactions
- Björn Rissiek (Hamburg, Germany) Immune cells from P2X4ko mice exhibit altered P2X7 expression and function
Content: Alterations of purinergic signals are associated with numerous disorders of cardiac and respiratory function, inflammation, chronic pain syndromes and various CNS diseases including neurodegenerative diseases associated with neuroinrenatflammation. Adenosine and purinergic receptors are expressed in various peripheral cell types as well as in various neuronal and glial cells within CNS, it is thus crucial to decipher the cell-specific function of each receptor in pathological contexts. We will cover in this symposium very recent and ongoing validation of new transgenic animal models and molecular tools useful to better understand P2X and adenosine receptor functions.
Title: Purines and purinergic receptors in vascular injury, cancer, and inflammation
Chairs: Evgenia Gerasimovskaya (Denver, USA) / Alexander Verin (Augusta, USA)
- Harry Karmouty-Quintana (UTHealth – McGovern Medical School, USA) Adenosine at the cross-roads of lung fibrosis and pulmonary hypertension”
- Mikhail Nikiforov (Wake Forest University, USA) Guanosine/Guanylate-Dependent Regulation of Signal Transduction in Cancer Cells
- Alexander Verin (Vascular Biology Center, Augusta University, USA) Dissecting the mechanisms of vascular barrier strengthening in acute lung injury: novel mechanisms for extracellular purines
- Evgenia Gerasimovskaya (University of Colorado Denver, USA) Extracellular ATP regulates angiogenic responses in vasa vasorum endothelial cells via the activation of PI3K-Akt-mTOR signaling axis and c-Jun, Foxo3a, and c-Myc transcription factors
Content: Extracellular purines are central, although still not fully recognized players in the vascular system. They control vascular cell growth, differentiation, permeability, inflammatory and immune responses. Inflammation plays a critical role in the vascular response to injury. Acute inflammation is characterized by increased vascular permeability and rapid accumulation of immune cells at the site of tissue injury and also associates with tumor progression. In addition, impaired vascular barrier function is frequently associated with dysregulated angiogenesis of immature and leaky microvessels, such as vasa vasorum, that serve as a conduit for the inflammatory cells into the vascular wall, thereby amplifying vascular inflammation process. In this symposium, we will highlight several research topics that demonstrate a role of extracellular adenosine, ATP and purine converting enzymes in a context of devastating vascular inflammatory disorders such as acute respiratory distress syndrome, pulmonary hypertension, diabetes and atherosclerosis. Moreover, novel data on detection, regulation and functional role of guanine, guanosine and guanosine phosphates in invasion and metastasis will be presented to underlie the importance of intracellular and extracellular purine signaling for cancer progression.
Title: New insights in P2X receptor structure-function
Chairs: Eric Boué-Grabot (Bordeaux, France) / Beata Sperlagh (Budapest, Hungary)
- Thomas Grutter (Strasbourg, France) Permeation mechanisms of large cations in ATP-gated P2X receptors
- Beata Sperlagh (Budapest, Hungary) Modulation of P2X7 receptor activity by extracellular Zn2+ – implications for mood disorders
- Philippe Séguéla (Montréal, Canada) Identification of a non-competitive antagonist site in P2X receptor-channels
- Fritz Markwardt (Halle, Germany) Structure-function relationship of P2X7 receptors.
Content: ATP-gated P2X receptors are trimeric ion channels selective to cations. In this symposium, we will cover recent advances in the understanding of the structure-function of several members of P2X receptor family in terms of ion permeation, antagonist sites and allosteric modulation.
Title: Adenosine-receptor containing complexes. From molecular dynamics and pharmacology to metabolism
Chairs: Kjell Fuxe (Stockholm, Sweden) / Rafael Franco (Barcelona, Spain)
- Vittorio Limongelli (Institute of Computational Science (ICS), University of Lugano USI, Switzerland / University of Naples, Italy) Unraveling the GPCR dimerization by second timescale free-energy calculations
- Alexander Pfeifer (PharmaZentrum, University of Bonn, Bonn, Germany) Role of adenosine in metabolism
- Dasiel Borroto-Escuela (Dept. Neurosciences, Karolinska Institute, Stockholm, Sweden) Adenosine heteroreceptor complexes in the basal ganglia are implicated in Parkinson disease and its treatment.
Gemma Navarro (Dept. Biochemistry and Physiology, University of Barcelona, Barcelona, Spain) Adenosine A2A receptor activation attenuate NMDA receptor function in Alzheimer disease
Content: Purinergic G-protein-coupled receptors (GPCRs) were among the first to be discovered forming complexes with other cell surface receptors. More recently, they have been instrumental to advance in the understanding of GPCR pharmacology and physiological role. This symposium covers dynamics of dimer formation, and the role of GPCR-GPCR and GPCR-ionotropic (NMDA) receptor heteromers in metabolism/obesity and in the CNS/neurodegeneration.
Title: Purinergic receptors and cancer
Chairs: Rosa Gomez-Villafuertes (Madrid, Spain) / Elena Adinolfi (Ferrara, Italy)
- Ruth Murrell-Lagnado (University of Sussex, UK) The role of the P2X4 receptor in breast cancer
- Elena Adinolfi (University of Ferrara, Italy) P2X7 receptor is a key regulator of ATP content and immune infiltration in the tumour microenvironment
- Ivana Novak (University of Copenhagen, Denmark) Role of purinergic signaling in pancreatic cancer
- Rosa Gomez-Villafuertes (Complutense University of Madrid, Spain) Regulation of P2X7 receptor gene expression in neuroblastoma cells
Content: Cancer is a major burden of disease worldwide. Each year, tens of millions of people are diagnosed with cancer around the world, and new disease markers and therapeutic targets are needed. P2 receptors are expressed by all tumours, in some cases to a very high level. Activation or inhibition of selected P2 receptor subtypes brings about cancer cell death or growth inhibition. This following symposium will try to show recent advances in the field of purinergic receptors in cancer development and progression.
Title: Structural insights into ligand binding and dynamics of P2X receptors
Chairs: Ralf Hausmann (Aachen, Germany) / Diego Dal Ben (Camerino, Italy)
- R. Schmid (Department of Molecular and Cell Biology, University of Leicester, Leicester, UK) Conformational change in P2XR – insights from molecular dynamics simulations
- J.P. Machtens (Computational Neurophysiology, ICS-4, Forschungszentrum Jülich, Jülich, Germany; Molecular Pharmacology, RWTH Aachen University, Aachen, Germany) The molecular dynamics of ion conduction in P2X receptors
- M.T. Young (School of Biosciences, Cardiff University, Cardiff, UK) The molecular determinants of small-molecule binding at P2X receptors
- D. Dal Ben (School of Pharmacy, University of Camerino, Camerino, Italy) Structural insights into modifications to the ATP molecule tuning its agonist-to-antagonist activity at the P2X receptors
Content: The publication of the hP2X3R structures in 2016 has created a solid basis for structural dynamics studies to provide further insights into the functioning of P2XRs. Molecular modelling, docking computations and molecular dynamics simulations allow us to gain a deeper understanding of how these ion channels function at the molecular level. These methods will facilitate molecular and atomistic insights into the mechanisms of ligand binding, gating, ion permeation and desensitization of P2XRs. Two talks will report on molecular dynamics simulations to provide insights into the closed-to-open and open-to-desensitized transition as well as ion permeation in P2XRs. The other two talks will focus on molecular modelling and docking computations to investigate molecular and structural determinants of small-molecule ligand binding and antagonist activity of novel ATP-derivatives. Thus, all talks will present computational studies including molecular modelling, ligand docking or molecular dynamics simulations to give structural insights into ligand binding and structural dynamics of P2XRs.
Title: Guanine-based purines in health and disease
Chairs: Francisco Ciruela (Barcelona, Spain) / Francesco Caciagli (Chieti, Italy)
- Victor Fernández-Dueñas (Institute of Neurosciences, University of Barcelona, Barcelona, Spain) Guanosine-induced neuroprotection: a role for adenosine receptor oligomers?
- Gennady Yegutkin (MediCity Research Laboratory, University of Turku, Turku, Finland) Extra- and intra-cellular metabolism of adenosine in cancer and inflammation
- Maria Grazia Tozzi (Department of Biology – Unit of Biochemistry, University of Pisa, Pisa, Italy) Impact of IMP-GMP specific 5’-nucleotidase on metabolic regulation and drug resistance in tumors
- Mariachiara Zuccarini (Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy) Conflicting effects of Guanosine, Guanine and their metabolizing enzymes on neuroprotection and tumor cell proliferation
Content: Guanine-based purines (GBPs) exert a multitude of beneficial (i.e., neuroprotective, neurotrophic, antidepressant, anxiolytic) effects throughout the CNS, being key players in cell metabolism and in several models of neurodegenerative disorders, such as Parkinson’s Disease (PD) and Alzheimer’s diseases (AD). Moreover, these compounds seem to be involved in tumor progression, and their converting enzymes can both activate some anti-cancer pro-drugs and play new patho-physiological roles independent of their enzymatic activities. Indeed, methyl-thyo-adenosine phosphorylase (MTAP) knockdown increases invasion and migration of several tumor cell lines; ii) an over-expression of the cytosolic 5’-nucleotidase (cN-II) has been observed in some cancer cells; iii) not frequent polymorphisms of gene encoding purine nucleoside phosphorylase (PNP) associated with a reduced enzymatic activity have been found in dysplastic or neoplastic alterations of marrow morphology or in prostate cancer. As no plasma-membrane receptor for GBPs have been described so far, these compounds are still considered orphan modulators of multiple functions, and many efforts should be made to elucidate the mechanism of action underlying their effects. In this context, the evaluation of the expression/activity of purine converting enzymes as well as the identification of specific receptors for GBPs could represent valuable diagnostic tools and innovative targets for the development of novel drugs and for new therapeutic approaches in neurological diseases and cancer. The talks of this symposium aim at giving a contribution to the knowledge of GBP roles in human diseases.
Title: Role for purines in bi-directional glia-neuron communications
Chairs: Yuriy Pankratov (Warwik, UK) / Alexei Verkhratsky (Manchester, UK)
- Rodrigo Cunha (Coimbra University, Portugal) ATP as a danger signal in the brain
- Yuriy Pankratov (University of Warwick, UK) ATP in astroglial control of synaptic plasticity in ageing and AD
- Arthur Butt (Portsmouth University, UK) Purinergic signalling in oligodendroglial lineage
- Rashid Giniatullin (University of Eastern Finland, Kuopio, Finland) Role for glial purinergic signalling in migraine
Content: Communication between neuronal and glial cells is fundamental for brain function. There is a growing evidence that ATP acts as a ubiquitous neurotransmitter in glial-neuronal, glial-glial and neuronal-glial communications both in physiological and pathophysiological contexts, Importantly, ATP (as well as other purines) can mediate bi-directional communication between neurones and glia: first, by activating Ca2+-signaling in glial cells via various P2 purinoceptors, and, in reverse, upon a release of various signalling molecules from astrocytes to modulate neuronal plasticity. Symposium speakers are international experts in most fundamental aspects of purinergic signalling integrating neuronal glial networks and contributing to neuropathology.
Title: P2X7: a common target for brain diseases?
Chairs: Miguel Diaz-Hernandez (Madrid, Spain) / Tobias Engel (Dublin, Ireland)
- Tobias Engel (Royal College of Surgeons in Ireland, Dublin, Ireland) Targeting of ATP-gated P2 receptors as novel treatment for drug-refractory epilepsy
- Annette Nicke (Ludwig-Maximilian University Munich, Munich, Germany) BAC transgenic mouse models to study P2X7 Expression and interactions
- Miguel Diaz-Hernandez (Universidad Complutense de Madrid, Madrid, Spain) Involvement of P2X7 receptor on the Alzheimer disease progression, therapeutic implications
- Jan Deussing (Max Planck Institute of Psychiatry, Munich, Germany). Validating P2X7R as risk factor for mood disorders
Content: Over the past recent years, the development of new transgenic animal models and highly specific pharmacological tools targeting the purinergic system has provided promising results in a great variety of different brain diseases. Purinergic signalling, in particular P2X7, has therefore gained an enormous interest, not only among brain researchers but also among pharma companies. Our symposium will include four experienced speakers at the forefront in their respective research field and who’s main interest constitutes the study of purinergic signalling, in particular P2X7. Our symposium will also include four talks from early stage researchers who will contribute with talks focusing on purinergic signalling in different brain diseases including topics on translational and basic research.
TITLE: Key roles of adenosine A2A receptors throughout brain development
Chairs: Rodrigo A. Cunha (Coimbra, Portugal) / Sabine Levi (Paris, France)
- Sara Alves Xapelli (University of Lisboa, Lisboa, Portugal) Adenosine A2A receptors and BDNF: an intimate interaction regulating postnatal hippocampal neurogenesis
- Ricardo Rodrigues (University of Coimbra, Coimbra, Portugal) Cortical neuronal migration entails A2A receptor-driven neuronal polarization and axon formation
- Catarina Gomes (ICBR, Coimbra, Portugal) Adenosine A2A receptor modulation of microglia morphologic remodeling in early neurodevelopment – gender bias in physiology and psychiatric disorders.
- Sabine Lévi (INSERM U1270, Paris, France) A2AR signalling regulates synaptogenesis in the developing brain
Content: Purinergic signaling mediated by ATP and adenosine plays an essential role in the nervous system where it mediates fast neurotransmission and neuromodulation. This symposium will highlight recent and important discoveries regarding the contribution of the adenosine signaling pathway in brain development. We have gathered four speakers who will present evidences that Adenosine A2A receptors govern neurogenesis, neuronal migration, axon formation and outgrowth, maintenance of newly formed synapses, and microglia morphology and function. Alterations in adenosine signaling during the critical period of development may lead to epilepsy, cognitive deficits and adult mood disorders.
Title: Role of purines in glial cell, proliferation, maturation and cell-to-cell communication in the central nervous system
Chairs: Felicita Pedata (Florence, Italy) / Ana Sebastião (Lisboa, Portugal)
- Marta Fumagalli (Milan Italy) Effects of ATP-induced microglial extracellular vesicles on oligodendrocyte progenitors in cerebral ischemia
- Etienne Audinat (Montpellier, France) Astrocyte purinergic signaling enhances excitatory synaptic transmission during epileptogenesis
- Sandra Vaz (Lisbon, Portugal) Role of astrocytic adenosine on the modulation of synaptic plasticity by BDNF
Young scientist attending the meeting:
- Stefano Raffaele (PhD student) Activated microglia regulate the response of oligodendrocyte progenitors expressing the P2Y-like receptor GPR17 following cerebral ischemia
- Federica Cherchi (Florence, Italy) The selective stimulation of adenosine A3 receptor inhibits N-type Ca2+ currents in rat dorsal root ganglion neurons
Content: This Symposium will integrate rapidly emerging information about the role of purinergic receptors expressed on astrocytes, oligodendrocytes and microglia as well as evidence for ATP-induced extracellular vesicles from glial cells. We will highlight the latest knowledge about the involvement of ATP and adenosine receptors in neuron–glia signalling, their functional significance under physiological and pathological conditions.
Title: Acupuncture and Purinergic Mechanism
Chair: Yong Tang (Chengdu, China)
- Wolfgang Schwarz (Goethe-University, Frankfurt, Germany) ATP release from mast cells by acupuncture stimuli
- Pei-Jing Rong (Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Science, Beijing, China) The role of purine receptor in the treatment of depression by taVNS
- Qiao-Feng Wu (SiChuan Provincial Hospital, Chengdu, China) Purinergic signaling in inflammatory bowel disease and its role in the effect of acupuncture and moxibustion
- Yong Tang (Chengdu University of Traditional Chinese Medicine, Chengdu, China) Purinergic signalling and acupuncture-induced analgesia
Content: Acupuncture is a Traditional Chinese Medicinal Therapy commonly used to combat pathological conditions notably pain. In 2009, the purinergic hypothesis of acupunctural analgesia was proposed by Geoffrey Burnstock: sensory nerve activity initiated in the skin by acupuncture would exert an inhibitory modulating effect on the spinoparabrachial and spinothalamic tracts to the brain pain centers. The hypothesis is supported by the early pharmacological finding that adenosine receptor antagonists theophylline and caffeine blocked the acupuncture-induced elevation of the nociceptive threshold. In 2010, the study by Maiken Nedergaard and colleagues provides the direct evidence that the acupuncture-released ATP is degraded to adenosine to produce analgesia via activation of adenosine A1 receptors. Since then, increasing evidence has demonstrated that purinergic signaling represent an important and crucial mechanism underlying the acupunctural analgesia. However, many central questions remain to be addressed experimentally to uncover the mode of the action of acupuncture. For example, are there dynamic changes in the concentrations of purines (ATP, ADP, AMP, adenosine) following acupuncture at the puncture site as well as pain-relevant areas of the brain? Is acupunctural analgesia mediated by purinergic signal at peripheral or central nerve systems? In addition to the A1 receptor, what are the contribution of other adenosine (such as A2A) and P2 receptors (such as P2X3, P2X4, and P2X7Rs) to acupunctural analgesia? Does purinergic signal interact with other nociceptive neuromodulators/receptors to modify acupunctural analgesia? This proposed symposium seeks to address these critical issues by scientists from multi-disciplines to provide the new insights into the purinergic mechanisms of acupuncture analgesia.
Title: Medicinal Chemistry of Purine Targets
Chairs: Christa E. Müller (Germany) / Bilha Fischer (Israel)
- Bilha Fischer (Israel) A Quest for a Disease Modifying Drug for the Treatment of Osteoarthritis-related Calcium Pyrophosphate Deposition Disease
- Hugo Gutierrez de Teran (Sweden) Integrated approaches to model the conformational equilibrium and the ligand optimization on adenosine receptors
- Eddy Sotelo (Spain) Evolutionary approaches for adenosine receptors modulation
- Anna Junker (Germany) P2 receptor ligands, PET tracers
Title: Impact of purinergic signalling in multiple sclerosis pathology
Chairs: Carlos Matute (Leioa, Spain) / María Domercq (Leioa, Spain)
- Claudia Verderio (CNR Institute of Neuroscience, Milan, Italy) Detrimental and protective action of microglial extracellular vesicles on myelin lesions: astrocyte involvement in remyelination failure
- Susana Mato (Achucarro Basque Center for Neuroscience and Department of Neuroscience, Leioa, Spain) Addressing the role of P2X7 receptors in primary demyelination and remyelination
- James S. Wiley (University of Melbourne, Melbourne, Victoria, Australia) The P2X7 receptor has a scavenger role in the central nervous system which is little affected by antagonists of P2X7 pore function
- Maria Domercq (Achucarro Basque Center for Neuroscience and Department of Neuroscience, Leioa, Spain) P2X4 receptor controls microglia activation and favours remyelination in autoimmune encephalitis
Content: Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by massive infiltration of immune cells, demyelination, and axonal loss. However, spontaneous myelin repair can occur during the course of the disease. A major component of this regenerative process is a robust innate immune response consisting of infiltrating macrophages and brain microgliosis. Therefore, specifically targeting myeloid cells could be an attractive therapeutic approach. Purinergic receptors control not only immune cell function together with the activation of microglia and astrocytes, but also neuronal and oligodendroglial survival in the pathology. Our symposium will include four different speakers talking about the role in MS of purinergic receptors, mainly P2X7 and P2X4. Claudia Verderio will focus on how microvesicles released by microglia in response to ATP influence oligodendrocyte progenitor cell function during remyelination. Susana Mato will talk about the role of P2X7 receptor in oligodendrocytes and microglia during primary demyelination. James Wiley will describe the scavenger activity of P2X7 receptors and its impact in MS disease. Finally, Maria Domercq’s talk will be focused on the role of P2X4 modulating microglia/macrophage inflammatory responses and promoting the repair of myelin damage.
Title: FIGHTING THE FIRE: novel purinergic approaches to manage immune-mediated disorders
Chairs: Luca Antonioli (Pisa, Italy) / Carmen Montesinos (Valencia, Spain)
- Pablo Pelegrin (Murcia BioHealth Research Institute-Hospital “Virgen de la Arrixaca” (IMIB-Arrixaca), Murcia, Spain) P2X7 receptor expression and function in human sepsis
- Ryszard T. Smolenski (Department of Biochemistry Medical University of Gdansk, Gdansk, Poland) Therapies targeting ectoenzymes of nucleotide breakdown in chronic inflammation related vascular pathologies
- Bruce Cronstein (NYU-H+H Clinical and Translational Science Institute Department of Medicine, NYU School of Medicine, New York, USA) Adenosine metabolism and receptors in osteoarthritis: targeting A2A receptors to reverse inflammaging
- Cinzia Volontè (CNR, IBCN, Rome, Italy) Targeting P2X7 in amyotrophic lateral sclerosis: where and when?
- Marco Idzko (Division of Pulmonology, Department of Medicine II, Medical University of Vienna, Vienna, Austria)
Content: Inflammation is a defense reaction aimed at eliminating the harmful agent from the organism and restoring tissue homeostasis. This process involves a series of immunological mechanisms able to modulate the activity of immune cells in order to preserve the integrity of our body. A number of studies revealed the critical role of the purine system (ATP and adenosine, mainly) in the modulation of inflammatory processes. Indeed, ischemia and hypoxic conditions at the inflammation site cause the release of high amounts of ATP, promoting the activation of the immune system through the interaction with purinergic receptors.
The present symposium will provide novel evidences about the role of purines in the pathophysiology of the inflammatory process, highlighting its potential as a possible target for the development of innovative strategies useful for the pharmacological treatment of immune-inflammatory disorders
Title: Teaching caffeine new tricks for old problems in Parkinson’s disease
Chairs: Luisa Lopes (Lisboa, Portugal) / Jiang-Fan Chen (Boston, USA)
- Jiang-Fan Chen (Boston School of Medicine, Boston, USA)
- Poul Jensen (Arrhus University, Arrhus, Denmark)
- Joana Coelho (iMM, Lisboa, Portugal)
Content: Caffeine and adenosine receptor ligands have been on trial against motor symptoms in Parkinson’s disease with very little efficacy, albeit their demonstrated benefits in epidemiological studies in patients. This hints at a predominant early, non-motor effect of the caffeine analogs that has been poorly discussed. We will cover very recent research and state-of-the-art tools that are providing new clues for these non-motor aspects, namely the effects on protein aggregation and spreading, receptor dimerization and cognition. We hope to contribute to a timely discussion while highlighting novel mechanisms that could be of general interest and applications beyond PD, to the wider neuropurine audience.