2017-Sustainable Industrial Processing Summit
SIPS 2017 Volume 2. Dodds Intl. Symp. / Energy Production

Editors:Kongoli F, Buhl A, Turna T, Mauntz M, Williams W, Rubinstein J, Fuhr PL, Morales-Rodriguez M
Publisher:Flogen Star OUTREACH
Publication Year:2017
Pages:306 pages
ISBN:978-1-987820-63-8
ISSN:2291-1227 (Metals and Materials Processing in a Clean Environment Series)
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    Oxidative Stress: from Life Sustainability to Life Unsustainability, from Blood Regulation in Brain to Alzheimer Disease

    Christian Amatore1;
    1CNRS & PSL, FRENCH ACADEMY OF SCIENCES, Paris, France;
    Type of Paper: General Plenary
    Id Paper: 300
    Topic: 46

    Abstract:

    Oxidative stress is well known by medical doctors and biologists for its negative health issues. Unfortunately, this knowledge is mostly based on long-time hard consequences on patients’ well-being and observation of specific protein markers or metabolites. Conversely, though less publicized than its negative aspects, oxidative stress is also necessary for sustaining aerobic life through a series of critical processes undergoing at the single cell or tissue levels. This explains why, starting with cyanobacteria, the evolution of aerobic cells and organisms has retained oxidative stress mechanisms while enforcing various mechanisms (enzymes, anti-oxidants, etc.) to maintain a delicate balance (homeostasis) between its positive and negative consequences.
    One good example of such delicate balance between life sustainability and life unsustainability is brought by the subtle mechanism of hyperemia that regulates blood distribution in the brain. Neurons cannot store the oxygen and nutrients amounts that are required to fulfil their high energy-demanding functions for more than 3-5 minutes (note that our brain consumes ca. 20 to 25% of our energy intake). Hence, when entering into a highly active status, neurons must send information to local blood capillaries to receive more energy than when less active. Besides its physiological function, the overall macroscopic outcome of this process allows observing the brain working through PET scans and functional magnetic resonance imaging (f-IRM). However, its fine details have long remained at the conjectural level. Thanks to the use of ultramicroelectrodes we have been able to investigate and quantitatively characterize this process and its dynamics at the level of single neurons. This confirmed that active neurons emit intense bursts of nitrogen monoxide (NO also known, though improperly, as ‘nitric oxide’) to entice local blood capillaries to deliver oxygen (O2) and nutrients. Hence, active neurons are usually bathed by an extracellular fluid simultaneously enriched in NO and O2.
    In the absence of copper-containing Amyloid-β (Cu-Aβ), this process is beneficial by allowing neurons to perform their functions. However, when free Cu-Aβ peptides accumulates locally, this is expected to lead to a fast-catalytic formation of peroxynitrite, a highly toxic species, near active neurons. When diffusing into neuron membranes, peroxynitrite initiates therein fast and intense free-radical propagating chains that eventually results in the apoptotic neuron death. Though overseen by the biological and medical communities, this mechanism may well be at the origin of Alzheimer’s disease. In this respect, rather than being a causative factor, the formation of amyloid plaques may represent the best way for the brain to protect its neurons, by decreasing the availability in highly deleterious free Cu-Aβ peptides.

    Keywords:

    Oxidation;

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    Amatore C. (2017). Oxidative Stress: from Life Sustainability to Life Unsustainability, from Blood Regulation in Brain to Alzheimer Disease. In Kongoli F, Buhl A, Turna T, Mauntz M, Williams W, Rubinstein J, Fuhr PL, Morales-Rodriguez M (Eds.), Sustainable Industrial Processing Summit SIPS 2017 Volume 2. Dodds Intl. Symp. / Energy Production (pp. 26-41). Montreal, Canada: FLOGEN Star Outreach