Talk by Z. Evgrafova at MLU (January 31, 2017)

Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers

The formation of amyloid fibrils is considered to be one of the main causes for many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s or Huntington’s disease [1]. Current knowledge suggests that amyloid-aggregation represents a nucleation-dependent aggregation process in vitro, where a sigmoidal growth phase follows an induction period. Here, we studied the fibrillation of amyloid β 1-40 (Aβ40) in the presence of thermoresponsive polymers, expected to alter the Aβ40 fibrillation kinetics due to their lower critical solution behavior [2-6]. To probe the influence of molecular weight and the end groups of the polymer on its lower critical solution temperature (LCST), also considering its concentration dependence in the presence of buffer-salts needed for the aggregation studies of the amyloids poly(methoxy di(ethylene  glycol)acrylates) with different LCSTs were synthesized. Mixtures and a conjugate of Aβ40 with these polymers in varying concentrations were studied via time-dependent measurements of the thioflavin T (ThT) fluorescence. The studies revealed that amyloid fibrillation was accelerated, accompanied by a reduction of the lag phase of Aβ40 fibrillation in the presence of the poly(methoxy di(ethylene glycol)acrylates) [6].

1. Chiti, F.; Dobson, C.M., Annu. Rev. Biochem. 2006, 75, 333–366.
2. Hamley, I.W., Angew. Chem. Int. Ed. 2007, 46, 8128–8147.
3. Hamley, I.W., Chem. Rev.2012, 112, 5147–5192.
4. Sgarbossa, A., Int. J. Mol. Sci. 2012.
5. Arosio, P.; Cukalevski, R.; Frohm, B.; Knowles, T.P.J.; Linse, S., J. Am. Chem. Soc. 2014, 136, 219–225.
6. Funtan, S.; Evgrafova, Z.; Adler, J.; Huster, D.; Binder, W.H., Polymers 2016, 8, 178.

Location: Von-Danckelmann-Platz 3, SR 1.03
Time: 3.30pm