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Metal chelator EGCG attenuates Fe( III )‐induced conformational transition of α‐synuclein and protects AS ‐ PC 12 cells against Fe( III )‐induced death
Author(s) -
Zhao Juan,
Xu Lihui,
Liang Qingnan,
Sun Qing,
Chen Congheng,
Zhang Yuan,
Ding Yu,
Zhou Ping
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14142
Subject(s) - chemistry , fibrillation , intracellular , reactive oxygen species , biophysics , chelation , fibril , biochemistry , microbiology and biotechnology , pharmacology , biology , medicine , atrial fibrillation , organic chemistry
The fibrillation and aggregation of α‐synuclein ( AS ), along with the conformational transition from random coil to β‐sheet, are the critical steps in the development of Parkinson's disease ( PD ). It is acknowledged that iron accumulation in the brain may lead to the fibrillation of AS . However, (‐)‐epigallocatechin gallate ( EGCG ) can penetrate the blood–brain barrier, chelate metal ions, and inhibit the fibrillation of amyloid proteins. Therefore, EGCG is warranted to be investigated for its potential to cure amyloid‐related diseases. In the present work, we sought to study the effects of EGCG on Fe( III )‐induced fibrillation of AS on both molecular and cellular levels. We demonstrate that Fe( III ) interacts with the amino residue of Tyr and Ala of AS , then accelerates the fibrillation of AS , and increases intracellular reactive oxygen species ( ROS ) in the AS transduced‐ PC 12 cells ( AS ‐ PC 12 cells). However, EGCG significantly inhibits this process by chelating Fe( III ) and protects AS ‐ PC 12 cells against the toxicity induced by ROS and β‐sheet‐enriched AS fibrils. These findings yield useful information that EGCG might be a promising drug to prevent and treat the neurodegenerative diseases.