A triple emission fluorescent probe reveals distinctive amyloid fibrillar polymorphism of wild-type alpha-synuclein and its familial Parkinson?s disease- mutants

CELEJ MS; CAARLS W; DEMCHENKO AP; JOVIN TM

ACS

Lugar: USA; Año: 2009 vol. 48 p. 7465 - 7465

ntracytoplasmic neuronal deposits containing amyloid fibrils of the 140-amino acid presynapticprotein R-synuclein (AS) are the hallmark of Parkinson?s (PD) disease and related neurodegenerative disorders. Three point mutations (A53T, A30P, and E46K) are linked to early onset PD. Compared to the wild-type (WT) protein, the mutants aggregate faster in vitro, but their fibrillar products are quite similar. Using the extrinsic multiple-emission probe 40-(diethylamino)-3-hydroxyflavone (FE), we demonstrate unique and distinct spectroscopic signatures for the amyloid fibrils formed by the WT and mutant AS, presumablyindicative of subtle differences in supramolecular structure. The two well-separated emission bands of the FE probe originate from a proton transfer reaction in the excited state. The ratiometric response constitutes a sensitive, tunable reporter of microenvironmental properties such as polarity and hydrogen bonding. The very distinctive fluorescence spectra of the F