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

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are both characterized by the formation and intraneuronal accumulation of fibrillar aggregates of α-synuclein (α-syn) protein in affected brain regions. α-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 α-, β-, and γ-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 α-syn from brain lysates. We also extracted low levels of β-syn from DLB brains, but failed to extract any γ-syn. We were able to capture only full-length monomeric α-syn from normal human CSF. Our data confirm the fatty acid binding properties of α-syn, and to a lesser extent β-syn, but suggest that γ-syn does not share this same characteristic.