[Frontiers in Bioscience 14, 376-397, January 1, 2009]

Vitagenes, dietary antioxidants and neuroprotection in neurodegenerative diseases

Vittorio Calabrese1, Carolin Cornelius1, Cesare Mancuso2, Eugenio Barone2, Stella Calafato1, Timothy Bates3, Enrico Rizzarelli1 and Albena T. Dinkova Kostova4

1Department of Chemistry, Biochemistry & Mol. Biology Section, Faculty of Medicine, University of Catania, Catania, Italy; 2Institute of Pharmacology, Catholic University School of Medicine, Roma, Italy; 3School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK; 4Division of Clinical Pharmacology, Departments of Medicine and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA and the Biomedical Research Centre, University of Dundee, Scotland, UK

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The vitagene family
3.1. Heme oxygenase-1
3.2. Heat shock protein 70
3.3. Thioredoxin/Thioredoxin reductase
4. Natural antioxidants and neurodegenerative disorders
4.1. Curcumin
4.2. Carnitines and acetyl-L-carnitine
4.3. Carnosine
5. Conclusions and perspectives
6. Acknowledgments
7. References

1. ABSTRACT

The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) heme oxygenase-1 and Hsp70, as well as the thioredoxin/thioredoxin reductase system. Heat shock response contributes to establish a cytoprotective state in a wide variety of human diseases, including inflammation, cancer, aging and neurodegenerative disorders. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Dietary antioxidants, such as curcumin, L-carnitine/acetyl-L-carnitine and carnosine have recently been demonstrated in vitro to be neuroprotective through the activation of hormetic pathways, including vitagenes. In the present review we discuss the importance of vitagenes in the cellular stress response and analyse, from a pharmacological point of view, the potential use of dietary antioxidants in the treatment of neurodegenerative disorders in humans.