ABSTRACT

Abstract..............................................................................................................277 17.1 Introduction..............................................................................................278 17.2 Neuroprotective Activity of Tea Catechins via Chelation of

Divalent Metals ........................................................................................280 17.2.1 Neuroprotective Effects In Vivo................................................280 17.2.2 Neuroprotective Effects In Vitro ...............................................281 17.2.3 Tea Catechins as Brain-Permeable, Nontoxic Iron

Chelators to “Iron Out” Iron from the Brain............................282 17.2.3.1 Effect of Tea Catechins on Iron and

Hypoxia-Regulated Genes .......................................287 17.2.4 Effects of Tea Catechins on Cell Signaling Pathways .............289

17.3 Conclusions..............................................................................................291 References .........................................................................................................291

Neurodegeneration in Parkinson’s, Alzheimer’s, or other neurodegenerative diseases appears to be multifactorial, in that a complex set of toxic reactions such as

oxidative stress, inflammation, glutamatergic neurotoxicity, reduced expression of trophic factors and endogenous antioxidants, dysfunction of the ubiquitinproteasome system with a concomitant accumulation of protein aggregates, and increase of nitric oxide, lead to the demise of neurons. A cardinal chemical pathology observed in these disorders is the accumulation of iron at sites where the neurons die. The buildup of an iron gradient in conjunction with reactive oxygen species (ROS) (superoxide, hydroxyl radical, and nitric oxide) is thought to constitute a major trigger of neuronal toxicity and demise in these diseases. Therefore, promising future treatment of neurodegenerative diseases and aging depends on the availability of effective brain-permeable, iron-chelatable/radical scavenger, neuroprotective drugs that will prevent the progression of neurodegeneration. Tea flavonoids (catechins) have been reported to possess potent divalent metal-chelating, antioxidant, and anti-inflammatory properties; to penetrate the brain barrier and to protect neuronal death in a wide array of cellular and animal models of neurological diseases. Additional mechanisms include activation of signaling pathways responsible for cell survival, growth, and differentiation. These activities make tea catechins promising substances for the treatment of brain deterioration during aging and neurodegeneration.