Publication: A new class of aggregation inhibitor of amyloid-beta peptide based on green tea catechins
Authors
Nieto Cerón, Susana
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Abstract
Alzheimer's disease (AD), the major dementing disorder of the elderly which accounts for 55% of all dementia patients worldwide, is related to amyloid-beta peptide, the main component of senile plaques in Alzheimer's disease brain. Observations suggest a broad ability for green tea catechins (GTC) to disrupt early-stage and late-stage aggregation processes but the molecular mechanism has not been fully elucidated. To advance the understanding of the potential use of GTC in the prevention or treatment of AD patients, we investigated the effect of natural and synthetic compounds on APP processing. We checked the ability of gallate containing phenolic compounds, including (-)-catechin, (-)- catechin gallate, (-)-epicatechin gallate, (-)-epigallocatechin, (-)-epigallocatechin gallate, gallic acid, and trimethoxy derivatives of epicatechin-3-gallate to inhibit acetylcholinesterase (AChE) activity and AChE-promoted Aβ aggregation. Compounds were analyzed for their ability to inhibit AChE by colorimetric and radiometric assays and for determining their type of enzyme inhibition. Fluorimetric studies with thioflavin T were performed to evaluate their effect on beta amyloid aggregation. We have found that TMCG, a 3,4,5-trimethoxy derivative of catechin gallate, exhibits a non competitive inhibition of AChE, has a disaggregating effect on amyloid fibrils and decreases the secretion of both 1-40 and 1-42 amyloid peptides to the extracellular medium of SH-SY5Y APP695 cell cultures. According to stability and bioavailability, methoxy derivates of catechins are promising drug to ameliorate the Alzheimer´s pathogenesis.
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Citation
The FEBS Journal, 2014
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