Abnormal migration of human wild-type α-synuclein upon gel electrophoresis

Abstract α-Synuclein aggregates have been linked to the pathogenesis of Parkinson's disease (PD), with Lewy bodies (LBs) and Lewy neurites (LNs) constituting the pathological hallmarks in the brains of patients with PD and dementia with LBs. LBs are formed by the conversion of soluble monomers of α-synuclein into insoluble aggregates. Here we report an abnormal electrophoretic mobility, at a higher molecular weight (MW) than the expected theoretical MW, of both recombinant histidine-tagged human α-synuclein, human α-synuclein expressed in SH-SY5Y human neuroblastoma cells or L tk − fibroblasts, and rat brain α-synuclein, on SDS–PAGE polyacrylamide, but not on Nu-PAGE gradient peptide, gels, suggesting possible α-synuclein data misinterpretations associated with gel electrophoresis. These studies raise important considerations about the type of protein gel electrophoresis system suitable to study the alterations of α-synuclein associated with neurodegeneration, PD and other synucleinopathies.