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      Curcumin, Hormesis and the Nervous System

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          Abstract

          Curcumin is a polyphenol compound extracted from the rhizome of Curcuma longa Linn (family Zingiberaceae) commonly used as a spice to color and flavor food. Several preclinical studies have suggested beneficial roles for curcumin as an adjuvant therapy in free radical-based diseases, mainly neurodegenerative disorders. Indeed, curcumin belongs to the family of hormetins and the enhancement of the cell stress response, mainly the heme oxygenase-1 system, is actually considered the common denominator for this dual response. However, evidence-based medicine has clearly demonstrated the lack of any therapeutic effect of curcumin to contrast the onset or progression of neurodegeneration and related diseases. Finally, the curcumin safety profile imposes a careful analysis of the risk/benefit balance prior to proposing chronic supplementation with curcumin.

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          Most cited references120

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          Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders.

          Despite the capacity of chaperones and other homeostatic components to restore folding equilibrium, cells appear poorly adapted for chronic oxidative stress that increases in cancer and in metabolic and neurodegenerative diseases. Modulation of endogenous cellular defense mechanisms represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. This article introduces the concept of hormesis and its applications to the field of neuroprotection. It is argued that the hormetic dose response provides the central underpinning of neuroprotective responses, providing a framework for explaining the common quantitative features of their dose-response relationships, their mechanistic foundations, and their relationship to the concept of biological plasticity, as well as providing a key insight for improving the accuracy of the therapeutic dose of pharmaceutical agents within the highly heterogeneous human population. This article describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including sirtuin and Nrf2 and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases. Particular attention is given to the emerging role of nitric oxide, carbon monoxide, and hydrogen sulfide gases in hormetic-based neuroprotection and their relationship to membrane radical dynamics and mitochondrial redox signaling.
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            The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse.

            Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk associates with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1beta, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta-amyloid (Abeta), soluble Abeta, and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease.
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              Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs

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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                10 October 2019
                October 2019
                : 11
                : 10
                : 2417
                Affiliations
                [1 ]Department of Biomedical and Biotechnological Sciences, University of Catania, Torre Biologica, Via Santa Sofia, 97–95125 Catania, Italy; mary-amir@ 123456hotmail.it (M.C.S.); btomase@ 123456unict.it (B.T.); marialaura.ontario@ 123456ontariosrl.it (M.L.O.); andreacavallaro@ 123456tiscali.it (A.C.); calabres@ 123456unict.it (V.C.)
                [2 ]Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; cesare.mancuso@ 123456unicatt.it
                [3 ]Institute of Pharmacology, Catholic University of Sacred Heart, 00168 Roma, Italy
                [4 ]Department of Clinical and experimental Medicine, Division of Endocrinology, University of Catania, 95125 Catania, Italy; f.frasca@ 123456unict.it
                [5 ]Department of Medical and Surgery Sciences, University of Catania, 95125 Catania, Italy; maiolino@ 123456policlinico.unict.it
                [6 ]Department of Environmental Health Sciences, School of Public Health and Health Science, University of Massachusetts, Amherst, MA 01003, USA; edwardc@ 123456schoolph.umass.edu
                Author notes
                [* ]Correspondence: trovato@ 123456unict.it
                [†]

                The authors contributed equally to this article.

                Author information
                https://orcid.org/0000-0003-1019-5158
                https://orcid.org/0000-0001-6049-942X
                https://orcid.org/0000-0002-0478-985X
                Article
                nutrients-11-02417
                10.3390/nu11102417
                6835324
                31658697
                f48c2455-727e-437a-9ce4-18ce011fdfd4
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 August 2019
                : 01 October 2019
                Categories
                Review

                Nutrition & Dietetics
                hormesis,vitagenes,antioxidants,heme oxygenase
                Nutrition & Dietetics
                hormesis, vitagenes, antioxidants, heme oxygenase

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