title: Bioactivity profiling with parallel mass spectrometry reveals an assemblage of green tea metabolites affording protection against human huntingtin and alpha-synuclein toxicity.
abstract: Aberrant protein aggregation and misfolding are key pathological features of many neurodegenerative disorders, including Huntington's and Parkinson's diseases. Compounds that offer protection from toxicity associated with aggregation-prone neurodegenerative proteins may have applications for the treatment of a multitude of disorders. A high-throughput bioassay system with parallel electrospray ionization mass spectrometry screening has been designed for critical evaluation of milligram quantities of natural product extracts, including dietary substances, for compounds of pharmacological relevance to the treatment of human neurodegenerative diseases. Using Saccharomyces cerevisiae strains engineered to express mutant human huntingtin and alpha-synuclein, we are able to identify extracts and compounds that protect cells from toxicity associated with these proteins. Applying this screening paradigm, we determined that a bioactive green tea extract contains an assemblage of catechins that were individually characterized for their respective protective effects against huntingtin and alpha-synuclein toxicity.
authors.affiliation: Natural Products Discovery Group, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, USA.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Williams
authors.forename: Will R
authors.initials: WR
authors.lastname: Gutekunst
authors.forename: P Matthew
authors.initials: PM
authors.lastname: Joyner
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Duan
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Todd D
authors.initials: TD
authors.lastname: Williams
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D002392:Catechin / Q000494:pharmacology; D006801:Humans; D000071058:Huntingtin Protein; D013058:Mass Spectrometry; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013662:Tea / Q000737:chemistry*; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010936:Plant Extracts; D011994:Recombinant Proteins; D013662:Tea; D051844:alpha-Synuclein; D002392:Catechin