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Green Tea Catechins Iron Chelator

Green tea catechins as brain-permeable, non toxic iron chelators
to ‘‘iron out iron’’ from the brain
S. Mandel, O. Weinreb, L. Reznichenko, L. Kalfon, T. Amit
Eve Topf and US NPF Centers for Neurodegenerative Diseases and Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel

J Neural Transm (2006) [Suppl] 71: 249–257

Summary Evidence to link abnormal metal (iron, copper and zinc) metabolism
and handling with Parkinson’s and Alzheimer’s diseases pathology
has frequently been reported. The capacity of free iron to enhance and
promote the generation of toxic reactive oxygen radicals has been discussed
numerous times. Metal chelation has the potential to prevent iron-induced
oxidative stress and aggregation of alpha-synuclein and beta-amyloid peptides.
The efficacy of iron chelators depends on their ability to penetrate the
subcellular compartments and cellular membranes where iron dependent
free radicals are generated. Thus, natural, non-toxic, brain permeable neuroprotective
drugs, are preferentially advocated for ‘‘ironing out iron’’ from
those brain areas where it preferentially accumulates in neurodegenerative
diseases. This review will discuss the most recent findings from in vivo and
in vitro studies concerning the transitional metal (iron and copper) chelating
property of green tea and its major polyphenol, ()-epigallocatechin-3-
gallate with respect to their potential for the treatment of neurodegenerative
diseases.

Introduction
The consumption of tea is believed to have been initiated
five thousands years ago in China and India (Gutman,
1996). In general, tea is consumed in the form of green
tea, oolong tea or black tea, which are all derived from
Camellia sinensis, a small plant grown mainly in China,
Japan and Southeast Asia. Green and black teas are differently
manufactured. Preservation of the intact green leaf is
of highest importance in the preparation of green tea. The
freshly harvested leaves are steamed to prevent fermentation
Abbreviations: AD Alzheimer’s disease; A amyloid beta peptide; APP
amyloid precursor protein; DA dopamine; DFO desferrioxamine; EGCG
()-epigallocatechin-3-gallate; HIF-1 hypoxia inducible factor-1; IRE iron
responsive element; IRP iron regulatory protein; MPTP N-methyl-4-phenyl-
1,2,3,6-tetrahydropyridine; 6-OHDA 6-hydroxydopamine; OS oxidative
stress; PD Parkinson’s disease; PKC protein kinase C; sAPP- soluble
APP-alpha; SN substantia nigra; Tf transferrin; TfR transferrin recepto