Protein aggregation and glycosaminoglycans.

ROSANA CHEHÍN

Paris

Congreso; 2nd European intensive Programo on Proteoglycans and glycosaminoglycans.; 2011

European Glycosaminoglicans society

Lewy bodies and Lewy neuritis, the neuropathological hallmarks of different neurological diseases, are mainly made of filamentous assemblies of α-synuclein. However, other macromolecules including tau, ubiquitin and glyceraldehyde-3-phosphate dehydrogenase and glycosaminoglycans are routinely found associated with these amyloid deposits. Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that can form fibrillar aggregates but its role in Parkinson’s disease is still unknown. In this work, the ability of heparin to trigger the amyloid aggregation of this protein at physiological conditions of pH and temperature is demonstrated by infrared and fluorescence spectroscopy, dynamic light scattering, small angle X-Ray scattering and fluorescence microscopy. Finally, we demonstrate that the early oligomers present in the glyceraldehyde-3-phosphate dehydrogenase fibrillation pathway promote α-synuclein aggregation recruiting α-synuclein toxic species toward to less toxic amyloid fibrils aggregates. The results presented herein suggest that heparin-induced glyceraldehyde-3-phosphate dehydrogenase early oligomers could be taken into account as a novel therapeutic strategy in Parkinson’s disease and other synucleinophaties.