An investigation into the lipid-binding properties of α-, β- and γ-synucleins in human brain and cerebrospinal fluid

Salem, Sultan A and Allsop, David and Mann, David M A and Tokuda, Takahiko and El-Agnaf, Omar M A (2007) An investigation into the lipid-binding properties of α-, β- and γ-synucleins in human brain and cerebrospinal fluid. Experimental Brain Research, 1170. pp. 103-111. ISSN 1432-1106

Abstract

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are both characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions. alpha-Syn has biochemical properties and a structural motif characteristic of fatty acid binding proteins. Using the fatty acid binding resin Lipidex-1000, we investigated the capture of alpha-, beta-, and gamma-syn proteins as lipid-associated proteins from normal and DLB brain lysates, and from normal human cerebrospinal fluid (CSF). These were eluted from Lipidex-1000 and analyzed by SDS-NuPAGE followed by Western blotting. Using this methodology, we have been able to extract full-length and truncated forms of alpha-syn from brain lysates. We also extracted low levels of beta-syn from DLB brains, but failed to extract any gamma-syn. We were able to capture only full-length monomeric alpha-syn from normal human CSF. Our data confirm the fatty acid binding properties of alpha-syn, and to a lesser extent beta-syn, but suggest that gamma-syn does not share this same characteristic.