An investigation into the lipid-binding properties of alpha-, beta- and gamma-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 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.
Salem
Sultan A
SA
Biomedical Sciences Unit, Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK.
Allsop
David
D
Mann
David M A
DM
Tokuda
Takahiko
T
El-Agnaf
Omar M A
OM
D001667:Binding, Competitive / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D003911:Dextrans / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism / Q000503:physiopathology; D008563:Membrane Lipids / Q000378:metabolism*; D051843:Synucleins / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism; D051846:beta-Synuclein / Q000378:metabolism; D051845:gamma-Synuclein / Q000378:metabolism
D003911:Dextrans; D008563:Membrane Lipids; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D051845:gamma-Synuclein; C010599:lipidex