Dataset Information

Insights into antiamyloidogenic properties of the green tea extract (-)-epigallocatechin-3-gallate toward metal-associated amyloid-? species.

ABSTRACT: Despite the significance of Alzheimer's disease, the link between metal-associated amyloid-? (metal-A?) and disease etiology remains unclear. To elucidate this relationship, chemical tools capable of specifically targeting and modulating metal-A? species are necessary, along with a fundamental understanding of their mechanism at the molecular level. Herein, we investigated and compared the interactions and reactivities of the green tea extract, (-)-epigallocatechin-3-gallate [(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate; EGCG], with metal [Cu(II) and Zn(II)]-A? and metal-free A? species. We found that EGCG interacted with metal-A? species and formed small, unstructured A? aggregates more noticeably than in metal-free conditions in vitro. In addition, upon incubation with EGCG, the toxicity presented by metal-free A? and metal-A? was mitigated in living cells. To understand this reactivity at the molecular level, structural insights were obtained by ion mobility-mass spectrometry (IM-MS), 2D NMR spectroscopy, and computational methods. These studies indicated that (i) EGCG was bound to A? monomers and dimers, generating more compact peptide conformations than those from EGCG-untreated A? species; and (ii) ternary EGCG-metal-A? complexes were produced. Thus, we demonstrate the distinct antiamyloidogenic reactivity of EGCG toward metal-A? species with a structure-based mechanism.

SUBMITTER: Hyung SJ

PROVIDER: S-EPMC3593904 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Insights into antiamyloidogenic properties of the green tea extract (-)-epigallocatechin-3-gallate toward metal-associated amyloid-β species.

Hyung Suk-Joon SJ DeToma Alaina S AS Brender Jeffrey R JR Lee Sanghyun S Vivekanandan Subramanian S Kochi Akiko A Choi Jung-Suk JS Ramamoorthy Ayyalusamy A Ruotolo Brandon T BT Lim Mi Hee MH

Proceedings of the National Academy of Sciences of the United States of America 20130220 10

Despite the significance of Alzheimer's disease, the link between metal-associated amyloid-β (metal-Aβ) and disease etiology remains unclear. To elucidate this relationship, chemical tools capable of specifically targeting and modulating metal-Aβ species are necessary, along with a fundamental understanding of their mechanism at the molecular level. Herein, we investigated and compared the interactions and reactivities of the green tea extract, (-)-epigallocatechin-3-gallate [(2R,3R)-5,7-dihydro ...[more]

PMID: 23426629

Similar Datasets

Project description:Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.

Dataset Information

Insights into antiamyloidogenic properties of the green tea extract (-)-epigallocatechin-3-gallate toward metal-associated amyloid-? species.

Publications

Insights into antiamyloidogenic properties of the green tea extract (-)-epigallocatechin-3-gallate toward metal-associated amyloid-β species.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets