Characterization of alpha-synuclein early aggregates by atomic force microscopy

JONATHAN A. FAUERBACH, DMYTRO YUSHCHENKO, ALEXANDER DEMCHENKO, THOMAS M. JOVIN, AND ELIZABETH A. JARES-ERIJMAN

San Francisco, California, Estados Unidos

Conferencia; Biophysical Society 54th Annual Meeting; 2010

Biophysical Society

Αlpha-synuclein (AS) is a key player in the development of Parkinson’s disease. Neither the mechanism of its aggregation nor its role in neurotoxicity have been established as yet. However, it has been proposed that early oligomeric species may be the most cytotoxic [1].Through the use of a covalently attached dual fluorescent emission ESIPT dye [2], we are able to monitor continuously the entire aggregation process in vitro [3]. Examination of samples by AFM has revealed a new pantheon of supramolecular species varying greatly in size and form. We identify a progression of structures starting from the unstructured monomer and proceeding through (i) spherical microaggregates (“fuzzy balls”); (ii) concatenated linear beaded fibrils (“fuzzy fibrils”); (iii) ring-like assemblies; (iv) circular “platforms” supporting nascent fibers [“acunas” = amyloid cunas (Spanish for cradle)]; and (v) terminal amyloid fibers [Figure 1].