Natural compounds against neurodegenerative diseases: molecular characterization of the interaction of catechins from green tea with Aβ1-42, PrP106-126, and ataxin-3 oligomers

Erika Sironi; Laura Colombo; Angela Lompo; Massimo Messa; Marcella Bonanomi; Maria Elena Regonesi; Mario Salmona; Cristina Airoldi

doi:10.1002/chem.201403188

Natural compounds against neurodegenerative diseases: molecular characterization of the interaction of catechins from green tea with Aβ1-42, PrP106-126, and ataxin-3 oligomers

Chemistry. 2014 Oct 13;20(42):13793-800. doi: 10.1002/chem.201403188. Epub 2014 Sep 1.

Authors

Erika Sironi¹, Laura Colombo, Angela Lompo, Massimo Messa, Marcella Bonanomi, Maria Elena Regonesi, Mario Salmona, Cristina Airoldi

Affiliation

¹ Department of Biotechnology and Biosciences University of Milano-Bicocca, P.zza della Scienza, 2, 20126, Milano (Italy), Fax: (+39) 02-6448-3565.

PMID: 25179684
DOI: 10.1002/chem.201403188

Abstract

By combining NMR spectroscopy, transmission electron microscopy, and circular dichroism we have identified the structural determinants involved in the interaction of green tea catechins with Aβ1-42, PrP106-126, and ataxin-3 oligomers. The data allow the elucidation of their mechanism of action, showing that the flavan-3-ol unit of catechins is essential for interaction. At the same time, the gallate moiety, when present, seems to increase the affinity for the target proteins. These results provide important information for the rational design of new compounds with anti-amyloidogenic activity and/or molecular tools for the specific targeting of amyloid aggregates in vivo.

Keywords: NMR spectroscopy; amyloid peptides; circular dichroism; molecular recognition; structure-activity relationship.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / metabolism*
Ataxin-3
Biological Products / chemistry
Biological Products / pharmacology
Catechin / chemistry
Catechin / pharmacology*
Flavonoids / chemistry
Flavonoids / pharmacology
Humans
Molecular Sequence Data
Nerve Tissue Proteins / chemistry
Nerve Tissue Proteins / metabolism*
Neurodegenerative Diseases / metabolism
Neurodegenerative Diseases / prevention & control*
Nuclear Magnetic Resonance, Biomolecular
Nuclear Proteins / chemistry
Nuclear Proteins / metabolism*
Peptide Fragments / chemistry
Peptide Fragments / metabolism*
Prions / chemistry
Prions / metabolism*
Protein Aggregation, Pathological / metabolism
Protein Aggregation, Pathological / prevention & control*
Repressor Proteins / chemistry
Repressor Proteins / metabolism*
Tea / chemistry*

Substances

Amyloid beta-Peptides
Biological Products
Flavonoids
Nerve Tissue Proteins
Nuclear Proteins
Peptide Fragments
Prions
Repressor Proteins
Tea
amyloid beta-protein (1-42)
prion protein (106-126)
flavan-3-ol
Catechin
ATXN3 protein, human
Ataxin-3