PMID- 22054421
OWN - NLM
STAT- MEDLINE
DCOM- 20120124
LR  - 20220318
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Linking)
VI  - 50
IP  - 49
DP  - 2011 Dec 13
TI  - Black tea theaflavins inhibit formation of toxic amyloid-beta and alpha-synuclein 
      fibrils.
PG  - 10624-36
LID - 10.1021/bi2012383 [doi]
AB  - Causal therapeutic approaches for amyloid diseases such as Alzheimer's and 
      Parkinson's disease targeting toxic amyloid oligomers or fibrils are still 
      emerging. Here, we show that theaflavins (TF1, TF2a, TF2b, and TF3), the main 
      polyphenolic components found in fermented black tea, are potent inhibitors of 
      amyloid-beta (Abeta) and alpha-synuclein (alphaS) fibrillogenesis. Their mechanism of action 
      was compared to that of two established inhibitors of amyloid formation, 
      (-)-epigallocatechin gallate (EGCG) and congo red (CR). All three compounds 
      reduce the fluorescence of the amyloid indicator dye thioflavin T. Mapping the 
      binding regions of TF3, EGCG, and CR revealed that all three bind to two regions 
      of the Abeta peptide, amino acids 12-23 and 24-36, albeit with different 
      specificities. However, their mechanisms of amyloid inhibition differ. Like EGCG 
      but unlike congo red, theaflavins stimulate the assembly of Abeta and alphaS into 
      nontoxic, spherical aggregates that are incompetent in seeding amyloid formation 
      and remodel Abeta fibrils into nontoxic aggregates. When compared to EGCG, TF3 was 
      less susceptible to air oxidation and had an increased efficacy under oxidizing 
      conditions. These findings suggest that theaflavins might be used to remove toxic 
      amyloid deposits.
FAU - Grelle, Gerlinde
AU  - Grelle G
AD  - Max Delbruck Centrum fur Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 
      Berlin-Buch, Germany.
FAU - Otto, Albrecht
AU  - Otto A
FAU - Lorenz, Mario
AU  - Lorenz M
FAU - Frank, Ronald F
AU  - Frank RF
FAU - Wanker, Erich E
AU  - Wanker EE
FAU - Bieschke, Jan
AU  - Bieschke J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111116
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Amyloid)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Antioxidants)
RN  - 0 (Biflavonoids)
RN  - 0 (alpha-Synuclein)
RN  - 1IA46M0D13 (theaflavin)
RN  - 3U05FHG59S (Congo Red)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
SB  - IM
MH  - Amyloid/*chemistry/drug effects/*metabolism
MH  - Amyloid beta-Peptides/chemistry/*metabolism
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Biflavonoids/*pharmacology
MH  - Binding Sites
MH  - Camellia sinensis/chemistry
MH  - Catechin/analogs & derivatives/*pharmacology
MH  - Cell Line, Tumor
MH  - Congo Red/pharmacology
MH  - Drug Evaluation, Preclinical/methods
MH  - Fluorescence
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Plaque, Amyloid/drug therapy
MH  - Protein Denaturation/drug effects
MH  - Rats
MH  - alpha-Synuclein/*metabolism
EDAT- 2011/11/08 06:00
MHDA- 2012/01/25 06:00
CRDT- 2011/11/08 06:00
PHST- 2011/11/08 06:00 [entrez]
PHST- 2011/11/08 06:00 [pubmed]
PHST- 2012/01/25 06:00 [medline]
AID - 10.1021/bi2012383 [doi]
PST - ppublish
SO  - Biochemistry. 2011 Dec 13;50(49):10624-36. doi: 10.1021/bi2012383. Epub 2011 Nov 
      16.