Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders.
Neurodegeneration in Parkinson's, Alzheimer's, or other neurodegenerative diseases appears to be multifactorial, where a complex set of toxic reactions, including oxidative stress (OS), inflammation, reduced expression of trophic factors, and accumulation of protein aggregates, lead to the demise of neurons. One of the prominent pathological features is the abnormal accumulation of iron on top of the dying neurons and in the surrounding microglia. The capacity of free iron to enhance and promote the generation of toxic reactive oxygen radicals has been discussed numerous times. The observations that iron induces aggregation of inert alpha-synuclein and beta-amyloid peptides to toxic aggregates have reinforced the critical role of iron in OS-induced pathogenesis of neurodegeneration, supporting the notion that a combination of iron chelation and antioxidant therapy may be one significant approach for neuroprotection. Tea flavonoids (catechins) have been reported to possess divalent metal chelating, antioxidant, and anti-inflammatory activities, to penetrate the brain barrier and to protect neuronal death in a wide array of cellular and animal models of neurological diseases. This review aims to shed light on the multipharmacological neuroprotective activities of green tea catechins with special emphasis on their brain-permeable, nontoxic, transitional metal (iron and copper)-chelatable/radical scavenger properties.
Mandel
Silvia
S
Eve Topf, Haifa, Israel. mandel@tx.technion.ac.il
Amit
Tamar
T
Reznichenko
Lydia
L
Weinreb
Orly
O
Youdim
Moussa B H
MB
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D016923:Cell Death; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000517:prevention & control; D009474:Neurons; D018696:Neuroprotective Agents; D013662:Tea / Q000737:chemistry*
D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D007501:Iron