Cellular Stress Response: A Novel Target for Chemoprevention and Nutritional Neuroprotection in Aging, Neurodegenerative Disorders and Longevity |
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Authors: | Vittorio Calabrese Carolin Cornelius Cesare Mancuso Giovanni Pennisi Stella Calafato Francesco Bellia Timothy E Bates Anna Maria Giuffrida Stella Tony Schapira Albena T Dinkova Kostova Enrico Rizzarelli |
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Institution: | Section of Biochemistry and Molecular Biology, Department of Chemistry, Faculty of Medicine, University of Catania, Viale Andrea Doria 6, 95100, Catania, Italy. calabres@unict.it |
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Abstract: | The predominant molecular symptom of aging is the accumulation of altered gene products. Moreover, several conditions including
protein, lipid or glucose oxidation disrupt redox homeostasis and lead to accumulation of unfolded or misfolded proteins in
the aging brain. Alzheimer’s and Parkinson’s diseases or Friedreich ataxia are neurological diseases sharing, as a common
denominator, production of abnormal proteins, mitochondrial dysfunction and oxidative stress, which contribute to the pathogenesis
of these so called “protein conformational diseases”. The central nervous system has evolved the conserved mechanism of unfolded
protein response to cope with the accumulation of misfolded proteins. As one of the main intracellular redox systems involved
in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective
heat shock proteins (Hsp) Hsp70 and heme oxygenase-1, as well as thioredoxin reductase and sirtuins. Nutritional studies show
that ageing in animals can be significantly influenced by dietary restriction. Thus, the impact of dietary factors on health
and longevity is an increasingly appreciated area of research. Reducing energy intake by controlled caloric restriction or
intermittent fasting increases lifespan and protects various tissues against disease. Genetics has revealed that ageing may
be controlled by changes in intracellular NAD/NADH ratio regulating sirtuin, a group of proteins linked to aging, metabolism
and stress tolerance in several organisms. Recent findings suggest that several phytochemicals exhibit biphasic dose responses
on cells with low doses activating signaling pathways that result in increased expression of vitagenes encoding survival proteins,
as in the case of the Keap1/Nrf2/ARE pathway activated by curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Consistently,
the neuroprotective roles of dietary antioxidants including curcumin, acetyl-l-carnitine and carnosine have been demonstrated through the activation of these redox-sensitive intracellular pathways. Although
the notion that stress proteins are neuroprotective is broadly accepted, still much work needs to be done in order to associate
neuroprotection with specific pattern of stress responses. In this review the importance of vitagenes in the cellular stress
response and the potential use of dietary antioxidants in the prevention and treatment of neurodegenerative disorders is discussed.
Special issue article in honor of Dr. Anna Maria Giuffrida-Stella. |
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Keywords: | Cellular stress response Redox homeostasis Aging Neurodegenerative disorders Vitagenes Antioxidants |
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