Redox Webinar Series 2022
Redox2022 Webinar detailed Programme
Thursday 15 December 2022 - Oxidative stress as a therapeutic target: from neurodegeneration to sickle cell disease
15:00-17:00 (Time Zone CET Europe/Rome)
Redox regulation of neurovascular coupling by nitric oxide to improve cognition
The brain is critically dependent on the rapid and transient delivery of bioenergetic substrates (oxygen and glucose) by the local vasculature to neighboring cells, according to energy demands imposed by neural activation. Failure of this process, the neurovascular coupling, either during aging and disease (Alzheimer´s disease) or following acute hypoxic conditions, compromises brain integrity and cognitive performance. The regulation of neurovascular coupling, a process involving the concerted cooperation of the cells comprising the neurovascular unit, is under the regulatory action of nitric oxide (NO) synthesized at glutamatergic synapses in hippocampus by the neuronal NO synthase isoform. Based in multimodal and molecular mechanistic approaches in vivo, I´ll provide evidences for novel redox couples that, by sustaining NO neurovascular messenger bioactivity, revert cognitive impairment in animal models of aging and neurodegeneration.
by João Laranjinha, University of Coimbra (Portugal)
João Laranjinha is professor of Biochemistry and Molecular Biology at the Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. He graduated in Pharmaceutical Sciences (University of Coimbra) in 1984 and got a PhD in Biochemistry (University of Coimbra) in 1996. He did Postdoc studies with Enrique Cadenas in 1997-1998 at the Dept. Molecular Pharmacology and Toxicology, University Southern California, Los Angeles, USA.
His research is focused on the functional impact of nitric oxide in the brain as a neurometabolic regulator and as a mediator of neurovascular coupling with impact in aging and neurodegeneration. He is also interested in dietary nitrite-driven regulatory processes, encompassing the non-enzymatic production of nitric oxide along the nitrate:nitrite:NO pathway. His laboratory has extensive expertise in the Biology & Biochemistry of free radicals, oxidants, antioxidants, in particular dietary polyphenols, and how a change of redox environment towards oxidation affects signaling pathways supporting a functional brain microcirculation and cognitive performance during aging. Overall, he has published 100+ papers in prestigious journals in the field and has coordinated circa 12 externally funded research projects, involving international teams.
He has been regularly invited to lecture at the major international meetings in the field, including SFRRI, OCC, Gordon Research Conference and FEBS meetings. More than 65 invited lectures during the last 20 years in Spain, Germany, Uruguay, Italy, Brazil, USA, Turkey, Switzerland, Argentina, France, India, Serbia, Slovakia, United Kingdom, Germany and Japan.
He has been awarded several prizes, including the Science and Humanity award by The Oxygen Club of California and is member of the editorial board of major journals in his area of research. He has chaired the organizing and scientific committees of several international conferences, including the European (SFRRE 2007) and International (SFRRI 2018) meetings of the Society for Free Radical Research. He has been member of the council of the European Society for Neurochemistry and the European Society for Free Radical Research for several years and President of the Portuguese Biochemical Society (2014-18). Currently, he serves as member of the Advanced Courses Committee of FEBS and as the president of the General Assembly of the Portuguese Biochemical Society.
Oxidative Stress and Hemolysis Dependent Destruction of Vascular Function in Sickle Cell Disease
Increased coagulation, homeostatic perturbation, adhesiveness of red and white blood cells to endothelium, all contribute to the vascular pathophysiology of sickle cell disease (SCD). The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall, and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. The occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Markers of hemolysis are also significantly increased in SCD patients compared to healthy controls and hemolytic rate has been shown to correlate closely with nitric oxide consumption and with the prevalence and severity of pulmonary hypertension. Recent findings showing reduced cholesterol levels and decreased sphingomyelin content in SCD can also influence increased susceptibility to hemolysis. Therapeutic strategies designed to counteract endothelial, inflammatory, and oxidative abnormalities may reduce the frequency of hospitalization and blood transfusion, the incidence of pain, and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.
by Mutay Aslan, Akdeniz University, Antalya (Turkey)
Professor Mutay Aslan MD., PhD. graduated from Çukurova University Faculty of Medicine and completed her medical residency training at Akdeniz University Faculty of Medicine, in Turkey. She received her Ph.D. in Biochemistry and Molecular Genetics from the University of Alabama at Birmingham, in the United States. She is currently working as a laboratory
supervisor at Akdeniz University Hospital and is also a lecturer at Akdeniz University Faculty of Medicine. Prof. Aslan currently serves as a member and was in the Management Committee of EU-COST. Dr. Aslan has been an independent expert/evaluator for the European Commission in selection of research proposals and has also been elected to the Advanced Courses Committee of The Federation of European Biochemical Societies (FEBS)
on January 2021 for a four-year term. Mutay Aslan continues her work in the Research and Diagnostic Lab at the Department of Medical Biochemistry at Akdeniz University. In recent years, Dr. Aslan has intensified her studies on lipoproteins, fatty acids and sphingolipids. Dr.
Aslan has 124 publications that have been published in peer-reviewed journals and a published patent. According to Google Scholar, these publications have 4774 citations and the h-index is 35.
Nanoceria particles are an eligible candidate to counteract oxidative stress preserving retinal morphology and function in an animal model of age-related macular degeneration (AMD)
As part of the central nervous system, the retina is particularly susceptible to alterations of its microenvironment, which can cause irreversible damage to vision. In addition, the retina, and especially the macula, is characterized by a state of physiological oxidative stress due to an elevated metabolism and high oxygen consumption. Hence, the maintenance of a correct and balanced microenvironment is fundamental in order to allow the health the retinal cells.
AMD occurs as a result of photoreceptor, retinal pigmented epithelium, Bruch’s membrane and choriocapillaris complex alterations, which culminates in blood retinal barrier breakdown, activation of inflammatory events and retinal neurodegeneration.
AMD can be considered a multifactorial disease and aging, cigarette smoke, high fat diet, light exposure, alcohol consumption, and specific genetic polymorphisms are considered the main risk factors. All these events share oxidative stress as a common feature that can be considered the driving force of all the risk factors.
Based on the absence of effective therapies for the treatment of AMD, in recent years important improvements have been made surrounding nanomedicine, which represents a promising research field due to the unmatched properties of nanoparticles. Cerium oxide nanoparticles (CeO2-NPs), a pure antioxidant, have been tested in our animal model of AMD and we demonstrated that the main features of AMD can be counteracted. Specifically, we have demonstrated their ability to preserve retinal function, to avoid the blood retinal barrier breakdown and debris accumulation, to counteract neovascularization and microglial activation.
Based on this evidence, it can be taken into consideration that CeO2-NPs may represent a promising therapeutical approach for AMD.
by Rita Maccarone, University of L'Aquila (Italy)
Her research field is focused on the functional study of the visual system and the mechanisms underlying retinal neurodegeneration. In particular, the scientific interest is focused on the degeneration of the neuroretina and retinal pigment epithelium, on the involvement of the retinal vascular system and on the breakdown of the haematoretinic barrier. The experimental approach consists of in vitro and in vivo studies in order to broaden the knowledge on the processes that lead to vision loss in the human diseases such as age-related macular degeneration with the aim of identifying effective neuroprotective strategies.
For many years she shared her interest in the physiopatology of the visual system with international research groups. She had an established collaboration with Prof. J. Stone and Prof. Kristztina Valter, of the "Australian National University", Canberra and the University of Sydney and with Prof. Kristrof Turlejsky, Nencky Institute, Warsaw, Poland.
She partecipated to several funded research projects (NATO Italy-Poland 2001, ASI 2001, CNR 2001, Boheringer 2002, PRIN 2000-2004-2006, POR Abruzzo 2004, International collaboration Italy - France 2005, Telethon).
more information will be available soon