Journal
BIOORGANIC CHEMISTRY
Volume 105, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2020.104382
Keywords
Alzheimer's disease; Amyloid beta-peptide; Polyphenol; Antioxidant; Green tea
Funding
- National Natural Science Foundation of China [21877059, 21201105]
- Natural Science Foundation of Jiangsu Province [BK20131200]
- Applied Research Program of Nantong City [BK2012012]
- Qing Lan Project of Jiangsu Province
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive accumulation of senile plaques, which are primarily composed of misfolded amyloid beta-peptide (A beta). A beta aggregates are believed to be a key factor in the pathogenesis of AD, affecting the nervous system in human body. The therapeutic potential of tea-derived polyphenolic compounds, (-)-epigallocatechin (EGC) and (-)-epicatechin-3-gallate (ECG), for AD was investigated by assessing their effects on the Cu2+/Zn2+-induced or self-assembled A beta(40) aggregation using thioflavine T fluorescent spectrometry, inductively coupled plasma mass spectrometry, UV-Vis spectroscopy, transmission electron microscope, silver staining, immunohistochemistry, and immunofluorescence assays. EGC and ECG mildly bind to Cu2+ and Zn2+, and diminish the Cu2+- or Zn2+-induced or self-assembled A beta aggregates; they also modulate the Cu2+/Zn2+-A beta(40) induced neurotoxicity on mouse neuroblastoma Neuro-2a cells by reducing the production of ROS. Metal chelating, hydrogen bonding or Van Der Waals force may drive the interaction between the polyphenolic compounds and A beta. The results demonstrate that green tea catechins EGC and ECG are able to alleviate the toxicity of A beta oligomers and fibrils. Particularly, ECG can cross the blood-brain barrier to reduce the A beta plaques in the brain of APP/PS1 mice, thereby protecting neurons from injuries. The results manifest the potential of green tea for preventing or ameliorating the symptoms of AD.
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