[Frontiers in Bioscience S4, 581-598, January 1, 2012]

The importance of the multiple target action of green tea polyphenols for neuroprotection

Silvia A. Mandel1, Orly Weinreb1, Tamar Amit1, Moussa B.H. Youdim1

1Eve Topf Center for Neurodegenerative Diseases Research and Department of Molecular Pharmacology, Faculty of Medicine, Technion, Haifa, Israel

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Epidemiological and clinical studies with black and green tea in Alzheimer's disease and Parkinson's disease
4. Neuroprotective studies with green tea
4.1. Preclinical in vivo data in aging and neurodegeneration models
4.2 .Preclinical cell culture studies
5. Mechanism of neuroprotective action of green tea polyphenol EGCG
5.1 . Iron chelation and antioxidant activity
5.1.1. Attenuation of Aβ, hyperphosphorylated τ and alpha-synuclein aggregation
5.1.2. Inhibition of APP translation
5.1.3. Modulation of iron-dependent hypoxia-inducible factor-1
5.2 . Modulation of cell signaling pathways
5.2.1. Activation of the protein kinase C (PKC) pathway
5.2.1.1 ...Prevention of apoptosis and mitochondrial dysfunction by EGCG
5.2.1.2. Regulation of APP and DA metabolism by EGCG
5.2.2 ..Modulation of other Signal Transduction Pathways
6. Combination therapy with green tea polyphenols targeting distinct brain pathologies
7. Perspective
8. References

1. ABSTRACT

Mounting evidence suggests that lifestyle factors, especially nutrition are essential factor for healthy ageing. However, as a result of the increase in life expectance, neurodegenerative diseases like Alzheimer's and Parkinson's (AD and PD, respectively) are becoming an increasing burden, as aging is their main risk factor. Brain aging and neurodegenerative diseases of the elderly are characterized by oxidative damage, dysregulation of redox metals homeostasis and inflammation. Thus, it is not surprising that a large amount of drugs/agents in therapeutic use for these conditions are antioxidants/metal complexing, bioenergetic and anti-inflammatory agents. Natural plant polyphenols (flavonoids and non-flavonoids) are the most abundant antioxidants in the diet and as such, are ideal nutraceuticals for neutralizing stress-induced free radicals and inflammation. Human epidemiological and new animal data suggest that green and black flavonoids named catechins, may help protecting the aging brain and reduce the incidence of dementia, AD and PD. This review will present salient features of the beneficial multi-pharmacological actions of black and green tea polyphenols in aging and neurodegeneration, and speculate on their potential in drug combination to target distinct pathologies as a therapeutic disease modification approach.