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      Anti-Apoptotic Effects of Carotenoids in Neurodegeneration

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          Abstract

          Apoptosis, programmed cell death type I, is a critical part of neurodegeneration in cerebral ischemia, Parkinson’s, and Alzheimer’s disease. Apoptosis begins with activation of pro-death proteins Bax and Bak, release of cytochrome c and activation of caspases, loss of membrane integrity of intracellular organelles, and ultimately cell death. Approaches that block apoptotic pathways may prevent or delay neurodegenerative processes. Carotenoids are a group of pigments found in fruits, vegetables, and seaweeds that possess antioxidant properties. Over the last several decades, an increasing number of studies have demonstrated a protective role of carotenoids in neurodegenerative disease. In this review, we describe functions of commonly consumed carotenoids including lycopene, β-carotene, lutein, astaxanthin, and fucoxanthin and their roles in neurodegenerative disease models. We also discuss the underlying cellular mechanisms of carotenoid-mediated neuroprotection, including their antioxidant properties, role as signaling molecules, and as gene regulators that alleviate apoptosis-associated brain cell death.

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          Most cited references156

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          The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress.

          A major mechanism in the cellular defense against oxidative or electrophilic stress is activation of the Nrf2-antioxidant response element signaling pathway, which controls the expression of genes whose protein products are involved in the detoxication and elimination of reactive oxidants and electrophilic agents through conjugative reactions and by enhancing cellular antioxidant capacity. At the molecular level, however, the regulatory mechanisms involved in mediating Nrf2 activation are not fully understood. It is well established that Nrf2 activity is controlled, in part, by the cytosolic protein Keap1, but the nature of this pathway and the mechanisms by which Keap1 acts to repress Nrf2 activity remain to be fully characterized and are the topics of discussion in this minireview. In addition, a possible role of the Nrf2-antioxidant response element transcriptional pathway in neuroprotection will also be discussed.
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            Overview of the IL-1 family in innate inflammation and acquired immunity.

            The interleukin-1 (IL-1) family of cytokines and receptors is unique in immunology because the IL-1 family and Toll-like receptor (TLR) families share similar functions. More than any other cytokine family, the IL-1 family is primarily associated with innate immunity. More than 95% of living organisms use innate immune mechanisms for survival whereas less than 5% depend on T- and B-cell functions. Innate immunity is manifested by inflammation, which can function as a mechanism of host defense but when uncontrolled is detrimental to survival. Each member of the IL-1 receptor and TLR family contains the cytoplasmic Toll-IL-1-Receptor (TIR) domain. The 50 amino acid TIR domains are highly homologous with the Toll protein in Drosophila. The TIR domain is nearly the same and present in each TLR and each IL-1 receptor family. Whereas IL-1 family cytokine members trigger innate inflammation via IL-1 family of receptors, TLRs trigger inflammation via bacteria, microbial products, viruses, nucleic acids, and damage-associated molecular patterns (DAMPs). In fact, IL-1 family member IL-1a and IL-33 also function as DAMPs. Although the inflammatory properties of the IL-1 family dominate in innate immunity, IL-1 family member can play a role in acquired immunity. This overview is a condensed update of the IL-1 family of cytokines and receptors.
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              Hydroperoxide metabolism in mammalian organs.

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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                29 July 2020
                August 2020
                : 25
                : 15
                : 3453
                Affiliations
                Department of Human Nutrition and Hospitality Management, College of Human Environmental Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA; mmhayden@ 123456crimson.ua.edu (M.M.H.); stbannerman@ 123456crimson.ua.edu (S.B.); jpjansen@ 123456crimson.ua.edu (J.J.); kcrowe@ 123456ches.ua.edu (K.M.C.-W.)
                Author notes
                [* ]Correspondence: hpark36@ 123456ches.ua.edu ; Tel.: +1-205-348-8051; Fax: +1-205-348-2982
                Author information
                https://orcid.org/0000-0001-5563-5255
                https://orcid.org/0000-0003-2497-4582
                Article
                molecules-25-03453
                10.3390/molecules25153453
                7436041
                32751250
                cbcc4fe5-1c0b-4ba6-8fe2-19290c0fd300
                © 2020 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
                : 06 July 2020
                : 27 July 2020
                Categories
                Review

                apoptosis,mitochondria,carotenoid,neurodegeneration,antioxidant

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