Evidence of Native α-Synuclein Conformers in the Human Brain

Background: -Synuclein aggregation is associated with Parkinson disease. The native state of -synuclein in the human brain is unclear. Results: Evidence consistent with the presence of conformationally diverse metastable multimers of -synuclein in the human brain is presented. Conclusion: Multimeric species of -synuclein are present within the human brain. Significance: Understanding the native state of -synuclein in the brain is critical for determining the causes or propensity for aggregation.-Synuclein aggregation is central to the pathogenesis of several brain disorders. However, the native conformations and functions of this protein in the human brain are not precisely known. The native state of -synuclein was probed by gel filtration coupled with native gradient gel separation, an array of antibodies with non-overlapping epitopes, and mass spectrometry. The existence of metastable conformers and stable monomer was revealed in the human brain.