Aβ42 (blue indicates monomers) collects inside cells and forms aggregates (green to red) after 24 hours. Chemistry and Biology, Esbjörner et al., Figure 4c.
Research led by Dr. Gabi Kaminski Schierle at this department reveals how Amyloid beta, a protein involved in Alzheimer's disease, develops into a pathogenic species.
The group has developed a fluorescent sensor concept (Kaminski Schierle GS, Bertoncini CW, Chan FTS, van der Goot AT, Schwedler S, Skepper J, Schlachter S, van Ham T, Esposito A, Kumita JR, Nollen EAA, Dobson CM, Kaminski CF, A FRET sensor for non-invasive imaging of amyloid formation in vivo, ChemPhysChem, 12(3), 673–680, (2011) ), which makes it possible to study how proteins misfold and aggregate in living cells.
Crucially it was shown that the kinetics of Abeta aggregation are vastly different in brain cells, than in the test tube, and further that the most pathogenic forms of Amyloid beta aggregate much faster in live cells than had previously been assumed from studies in test tubes. The technique makes it possible to correlate the appearance of certain aggregate species with their gain of toxic function thus providing a tool to screen for potential therapeutic agents in more efficient ways than hitherto possible.
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Esbjörner EK, Chan F, Rees E, Erdelyi M, Luheshi LM, Bertoncini CW, Kaminski CF, Dobson CM, Kaminski Schierle GS. Direct observations of amyloid β self-assembly in live cells provide insights into differences in the kinetics of Aβ(1–40) and Aβ(1–42) aggregation. Chemistry & Biology. 2014 May 22. [Epub ahead of print]