Purinergic frontiers: from basic science to clinical challenges

The main purpose of this symposium is to offer an updated view of the purinergic field, in which advances in basic research have paved the way for a better understanding of the pathophysiology of a variety of diseases and, as a consequence, have generated new possibilities for clinical interventions. Among the topics that will be covered are inflammation, chronic pain, cancer, and neurodegenerative diseases.

The symposium will start with an opening lecture by Geoffrey Burnstock, the scientist who discovered -and also coined the term- purinergic transmission in the 1970s. It is, therefore, a unique occasion to learn the living history of this area while emphasizing the recent advances regarding the therapeutic potential of purinergic signaling.

The following lectures will certainly facilitate a thorough understanding of the role of purinergic signaling in neural function and neurological and neurodegenerative diseases by addressing issues, such as:

Another group of lectures will be focused on the role of purinergic receptors in pain and inflammation. Pathological neuroplasticity (central and peripheral sensitization) of the nociceptive pathway, ultimately leading to neuropathic pain, has been associated with genetic variability of purinergic receptors expressed by reactive spinal microglia. Moreover, nucleotide and dinucleotide compounds have also been described as very effective treatments in ocular painful inflammatory processes as well as in corneal ulcers. A different type of ocular pathology, such as glaucoma, is also being considered by treatment with purinergic agents.

A new prostaglandin pathway controlling purinergic signaling has been recently discovered in macrophages, which may make possible novel interventions of the innate immune response. It should be remembered that the first line of defense against infections by intracellular pathogens involves stimulation of innate immunity. In this regard, studies confirming the participation of purinergic signaling in the response to protozoa (Plasmodium, Leishmania and Trypanosoma) infections causing prevalent neglected diseases, will also be presented in the symposium.

The identification of new targets potentially relevant for the treatment of specific diseases has to be accompanied by medicinal chemistry studies aiming at the discovery of compounds able to interact with such targets. The first purinergic pharmaceuticals were analogs of natural purine nucleosides that had application in cancer chemotherapy due to their ability to serve as substrates of specific cell membrane transporters. Nowadays, slight chemical modifications of these chemical structures resulting in altered substrate-transporter interactions along with the analysis of transporter distribution in epithelial barriers and target cells continue to favor a deeper knowledge of the key elements determining the pharmacokinetics and pharmacodynamics of many purinergic drugs. Furthermore, X-ray crystallographic analyses of G protein-coupled receptors for adenosine and nucleotides are providing new insights for the design of selective agents useful for the therapy of viral infections and inflammatory diseases (e.g., inflammatory bowel disease), or as a new generation of antithrombotics, vascular remodeling drugs, and antigenotoxic stress compounds.

These are the frontiers of the purinergic world today. By bringing together international experts, this symposium offers the opportunity to acquire first-hand information to understand this continuously expanding field and forecast its brilliant future with regard to therapeutic drug development.