FLOGEN

FLOGEN SIPS 2022: Yoshikawa International Symposium on Oxidative Stress for Sustainable Development of Human Beings (2nd international Symposium) Presenter: Prof. Nektarios Tavernarakis, University of Crete, Heraklion, Greece Title: Cellular energy homeostasis in neurodegeneration and ageing Abstract Ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital for proper cellular function. Although this process is fundamentally haphazard and uncontrollable, senescent decline and ageing is broadly influenced by genetic and extrinsic factors. Numerous gene mutations and treatments have been shown to extend the lifespan of diverse organisms ranging from the unicellular Saccharomyces cerevisiae to primates. It is becoming increasingly apparent that most such interventions ultimately interface with cellular stress response mechanisms, suggesting that longevity is intimately related to the ability of the organism to effectively cope with both intrinsic and extrinsic stress. Key determinants of this capacity are the molecular mechanisms that link ageing to main stress response pathways, and mediate age-related changes in the effectiveness of the response to stress. How each pathway contributes to modulate the ageing process is not fully elucidated. A better understanding of the dynamics and reciprocal interplay between stress responses and ageing is critical for the development of novel therapeutic strategies that exploit endogenous stress combat pathways against age-associated pathologies. Mitochondria, the indispensable and highly dynamic, energy-generating organelles in all eukaryotic cells, play essential roles in fundamental cellular processes. Neuronal cells depend, perhaps more than any other cell type, on proper mitochondrial function. Mitochondrial impairment is a major hallmark of several age-related neurodegenerative pathologies, including Alzheimer’s disease. Interestingly, accumulation of damaged mitochondria has been observed in post-mortem brain of Alzheimer’s disease patients. Mitophagy is a selective type of autophagy mediating elimination of damaged mitochondria, and the major degradation pathway, by which cells regulate mitochondrial number in response to their metabolic state. However, little is known about the role of mitophagy in the pathogenesis of Alzheimer’s disease. Although disease-associated tau and amyloid β are known to deregulate mitochondrial function, it remains elusive whether they also directly influence the efficiency of mitophagy. To address this question, we developed an in vivo imaging system to monitor mitophagy in neurons. We demonstrated that neuronal mitophagy is impaired in C. elegans models of Alzheimer’s disease. Urolithin A- and nicotinamide mononucleotide-induced mitophagy ameliorates several pathological features of Alzheimer’s disease, including cognitive defects. Mitophagy stimulation restores memory impairment. Age-dependent decline of mitophagy both inhibits removal of dysfunctional or superfluous mitochondria and impairs mitochondrial biogenesis resulting in progressive mitochondrial accretion and consequently, deterioration of cell function. Our findings suggest that impaired removal of damaged mitochondria is a pivotal event in Alzheimer’s disease pathogenesis highlighting mitophagy as a potential therapeutic intervention.

FLOGEN SIPS 2022: Yoshikawa International Symposium on Oxidative Stress for Sustainable Development of Human Beings (2nd international Symposium) Presenter: Prof. Christian Andre Amatore, CNRS & PSL, French Academy of Sciences, Paris, France Title: Nanometer-sized electrochemical probes for intracellular measuring ROS/RNS in single cells and cellular organelles Abstract Oxidative stress conditions are encountered by all aerobic organisms during their whole life. Indeed, aerobic cells mostly derive their energy from the intracellular enzyme-catalyzed oxidation of fat and sugars to CO2. Also, metalloenzymes which are central actors of the respiratory chain in mitochondria are generally good reducing agents, prone to open side routes leading to O2 reduction to superoxide ion (O2•-) that is the precursor of a series of hazardous species collectively named as “reactive oxygen species (ROS)” and “reactive nitrogen species (RNS)” [1,2]. ROS and RNS may induce molecular damages to almost all organic compounds performing biological functions (nucleic acids, proteins, cells carbohydrates and lipids, etc.) – a situation termed “oxidative stress” when it runs out of control. Even without exposure to radiation or other photo-biological effects, oxidative stress can bring about such pathological conditions as inflammation, carcinogenesis, Parkinson and Alzheimer diseases, and various autoimmune illnesses, as well as accelerated ageing. The primary ROS/RNS, viz., hydrogen peroxide, peroxynitrite ion, nitric oxide, and nitrite ion, can be oxidized at different electrode potentials and therefore detected and quantified by electroanalytical techniques [3]. Nanometer-sized electrochemical probes with cylindrical shapes do not experience this problem since they can penetrate across the cell membranes that reseal around their shaft (7). They are then especially suitable for measuring ROS/RNS in single cells and cellular organelles. In this paper, we will survey recent advances in localized measurements of ROS/RNS inside single cells. Application of this method will be presented for detection of ROS/RNS in phagolysosomes during phagocytosis by macrophages (4,5). We will also evidence using these methods that remediation of Oxidative Stress in neurons artificially placed under Parkinson Disease conditions avoids the impeachment of synaptic communication when the neurons are pre-treated with Harpagide, a natural sugar derivative which alleviate the oxide stress borne by mitochondria (9). References: (1) B. Halliwell, J.M.C. Gutteridge, Free Radicals in Biology and Medicine, 3rd ed., Oxford University Press, Oxford, 1999. (2) F. Murad: Discovery of Some of the Biological Effects of Nitric Oxide and its Role in Cell Signaling. Nobel Lecture for Medicine, 1998, https://www.nobelprize.org/uploads/20... (3) C Amatore, S. Arbault, M. Guille, F. Lemaître: Electrochemical monitoring of single cell secretion: vesicular exocytosis and oxidative stress. Chem. Rev. 108 (2008) 2585–2621. (4) K. Hu, Y.L. Liu, A. Oleinick, M.V. Mirkin, W.H. Huang, C. Amatore: Nanoelectrodes for Intracellular Measurements of Reactive Oxygen and Nitrogen Species in Single Living Cells. Curr. Opin. Electrochem., 22, 2020, 44-50, and refs therein. (5) Y.T. Qi, H. Jiang, W.T. Wu, F.L. Zhang, S.Y. Tian, W.T. Fan, Y.L. Liu, C. Amatore, W.H. Huang: Homeostasis Inside Single Activated Phagolysosomes: Quantitative and Selective Measurements of sub-Millisecond Dynamics of ROS/RNS Production with a Nanoelectrochemical Sensor. J. Am. Chem. Soc., 144, 2022, 9723-9733.

FLOGEN SIPS 2022: Yoshikawa International Symposium on Oxidative Stress for Sustainable Development of Human Beings (2nd international Symposium) Presenter: Prof. Koji Fukui, Shibaura Institute of Technology, Saitama, Japan Title: Twendee X improves cognitive function in vitamin E-deficient mice Abstract Reactive oxygen species may attack several living organs and gradually accumulate oxidative products such as lipid hydroperoxides. Recently, several kinds of evidence have been demonstrated that accumulation of oxidative products induces onset and progression of several severe diseases such as inflammations, cardiovascular events and more [1]. One severe disease is dementia, and it also deeply relates to senescence. To prevent age-related neurodegenerative disorders, treatment with antioxidant is effective. Twendee X, a mixed antioxidant supplement contains 8 substances [2] and anyone can buy it. However, the detailed scientific evidence is not enough. In this study, we fed Twendee X to vitamin E-deficient mice and check cognitive function. We created vitamin E-deficient mice and Twendee X treated for one month. Cognitive function was measured by the Morris Water maze task [3]. Vitamin E deficient mice were significantly decrease learning ability. Treatment with Twendee X was significantly improved it. Brain neurotrophic factors in Twendee X-treated mouse were significantly increase compared to the untreated groups. Twendee X has a potential as a powerful antioxidant supplement through protection against neuronal dysfunction. References: [1] Yoshida, N, Kato, Y, Takatsu, H, et al., Biomedicines 10 (2022) 28. [2] Tadokoro, K, Morihara, R, Ohta, Y, et al., J Alzheimer’s Dis, 71 (2019) 1063-1069. [3] Fukui, K, Onodera, K, Shinkai, T, et al., Ann NY Acad Sci, 928 (2001) 169-176.

FLOGEN SIPS 2022: Yoshikawa International Symposium on Oxidative Stress for Sustainable Development of Human Beings (2nd international Symposium) Presenter: Dr. Alexander Oleinick, CNRS, Paris, France Title: Modelling detection of key biomolecules with enzymatic electrodes: Diffusion towards randomly distributed active sites Abstract Monitoring of key biomolecules and/or oxidative stress at cellular or sub-cellular levels by means of electrochemistry requires electrodes with good selectivity and sensitivity. These both characteristics often achieved by employing enzymatic electrodes. At these electrodes the enzymes are generally dispersed within a polymer layer covering electrode surface, where product(s) of the enzymatic conversion are detected. Rationalization of the experimental data imply understanding mass transport towards an enzymatic electrode which is a complicated process due to random distribution of the enzymes along the electrode surface. This process can be considered through the framework of random arrays, that is a set of active sites distributed randomly, which is also useful for description of many practical micro- and nanoscale systems [1]. As shown previously these systems can be efficiently addressed theoretically by using Voronoi diagrams [1, 2] which allows facile tessellation of the system into the unit cells around each active sites. The overall current flowing in the system can then be evaluated by modelling diffusion-reaction processes inside every unit cell and summing the contributions from individual active sites. Although this approach is tempting by its simplicity and efficiency [1] one should bear in mind that Voronoi diagram representing the unit cells by polygonal prisms remains approximation and as each approximation remains valid only under certain conditions. We have shown [3] that even for the case of diffusion limited electron transfer (ET) the actual shapes of the unit cells are more complicated and depend on the local configuration of the neighbouring active sites. This was exemplified on the small patches of the random arrays with band-like and disk-like active sites via simulations and analytical derivations. Importantly, by comparing the total and individual electrode currents obtained by employing Voronoi tessellation and simulation of the system without any approximations we found that the former are reproduced with a good accuracy while the latter are evaluated with a much larger relative error [3], thus demonstrating the limits of Voronoi tessellation for representation of such systems. Moreover, diffusion interaction between the neighbouring sites compensate the differences in unit cell sizes leading to a more uniform unit cell sizes then predicted by Voronoi tessellation [4]. This, in particular explains why the early theory of random arrays using uniform representation of the system were quantitatively successful [5]. References: [1] O. Sliusarenko, A. Oleinick, I. Svir, C. Amatore. J. Electrochem. Soc. 167, 2020, 013530. [2] T. J. Davies and R. G. Compton. J. Electroanal. Chem. 585, 2005, 63. [3] G. Pireddu, I. Svir, C. Amatore, A. Oleinick, ChemElectroChem 8, 2021, 2413. [4] G. Pireddu, I. Svir, C. Amatore, A. Oleinick, Electrochim. Acta 365, 2021, 137338. [5] C. Amatore, J.-M. Savéant, D. Tessier, J. Electroanal. Chem. 147, 1983, 39.

FLOGEN SIPS 2022: Yoshikawa International Symposium on Oxidative Stress for Sustainable Development of Human Beings (2nd international Symposium) Presenter: Prof. Shigeru Hirano, Kyoto Prefectural University of Medicine, Kyoto, Japan Title: Role of Anti-Oxidant Twendee X for Maintenance of Voice and Swallow Abstract Voice and swallowing function are critical functions for human life which is supported by intriguing motion of pharynx and larynx. Swallowing function is complicated consisting of the motion of tongue, soft palate, pharyngeal muscles, laryngeal elevation, and the vocal folds. Reactive oxygen species (ROS) affects the whole organs and their functions, which deteriorate vocal and swallowing function with age or diseases. Dysphagia causes sarcopenia, frail, and aspiration pneumonia which occasionally causes death. It is important to maintain swallowing function as well as vocal function to keep the body in healthy status. Twendee X, the strongest anti-oxidant, can maintain the function of the pharynx and larynx by reducing ROS. Our previous data indicated that reduction of ROS leads to maintenance of the vocal folds against aging or injury. We have also confirmed that Twendee X can maintain the vocal function of professional singers. To date, we have established a dysphagia model of guinea pig by resecting nerve branches to the thyropharyngeal muscle. This model represents motor-related dysphagia which is often observed in elderly or patients with neuromuscular diseases. In this model, the animals became unable to eat immediately after the surgery, and lost weight for about 1 week, but they recovered by compensation. When the animals were fed with Twendee x, the immediate reduction of food intake was prevented possibly because of maintenance of the muscles. Twendee X is thought to be effective for maintenance of voice and swallowing function.

Playa Bonita - SIPS 2023 Venue - Beautiful View of early morning and late evening with a line up of big boats on line to pass the Panama Canal

FLOGEN SIPS 2023 Promotion

Dancing with Embera Quera indigenous community in Gatun River in Panama . Amazing idyllic reality

Dancing with Embera Quera indigenous community in Gatun River in Panama . Amazing idyllic reality