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CeNS Colloquium

Place: Kleiner Physik-Hörsaal, Geschwister-Scholl-Platz
Date: 03.07.09, Time: 15:30 h

The molecular basis of Parkinson's disease. Nanoparticles and other probes track the conformational transitions of alpha-synuclein from a monomer to amyloid aggregates

Thomas M. Jovin
Laboratory of Cellular Dynamics, MPI f. Biophysical Chemistry, Göttingen
Laboratorio Max Planck de Dinámica Celular, Universidad de Buenos Aires


In a study [1] conducted together with colleagues of the University of Buenos Aires, Argentina (laboratory of Elizabeth Jares-Erijman), quantum dots (QDs) carrying a-synuclein (AS), a protein whose aggregation in brain neurons is presumed to be the major cause of Parkinson's disease, were shown to serve as very effective dual sensors and seeds of aggregation, both in vitro and in vivo. The efficiency of the QD-AS complexes depends on the loading density (protein molecules/QD) and they act at the very low relative (to total protein) concentration of 10-5-10-4. A quantitative analysis of the in vitro data has led to the determination of a "nucleation enhancement factor" accounting for the enhancement of aggregation.

Other probes developed for this and other related studies have included AS fused to a tetracysteine tag specific for biarsenicals [2], covalent pyrene derivatives of AS [3], and other extrinsic and covalent environment sensitive indicators: aminonaphthalene sulfonates [4] and excited state proton transfer (ESIPT) reagents. Used together with AFM, DLS, NMR, and electrochemical determinations, such tools are enabling the identification and characterization of the elusive, yet presumably cytotoxic, intermediates of amyloid aggregation.

In a further collaboration with the Jares-Erijman group (PhD student Guillermo Menéndez), a pH sensor consisting of a quantum dot and pH indicators bound to its surface has been developed. Time-resolved emission measurements indicate the operation of numerous photophysical processes, including pH-dependent bidrectional FRET, accounting for a linear variation of the mean fluorescence lifetime over the wide pH range of pH 4-10.


[1] M. J. Roberti et al., J. Am. Chem. Soc. 2009, 131, 8102-8017.
[2] M. J. Roberti et al., Nat. Methods 2007, 4, 345-351.
[3] Thirunavukkuarasu, S et al., J. Mol. Biol. 2008, 378, 1064-1073.
[4] Celej, M. S et al., Biophys. J. 2008, 94, 4867-4879.