title: Characterization of oligomerization-aggregation products of neurodegenerative target proteins by ion mobility mass spectrometry.
abstract: Protein amyloidogenesis is generally considered to be a major cause of two most severe neurodegenerative disorders, Parkinson's disease (PD) and Alzheimer's disease (AD). Formation and accumulation of fibrillar aggregates and plaques derived from α-synuclein (α-Syn) and ß-amyloid (Aß) polypeptide in brain have been recognized as characteristics of Parkinson's disease and Alzheimer's disease. Oligomeric aggregates of α-Syn and Aß are considered as neurotoxic intermediate products leading to progressive neurodegeneration. However, molecular details of the oligomerization and aggregation pathway(s) and the molecular structure details are still unclear. We describe here the application of ion-mobility mass spectrometry (IMS-MS) to the identification of α-Syn and Aß oligomerization-aggregation products, and to the characterization of different conformational forms. IMS-MS is an analytical technique capable of separating gaseous ions based on their size, shape, and topography. IMS-MS studies of soluble α-Syn and Aß-aggregates prepared by in vitro incubation over several days were performed on a quadrupole time of flight mass spectrometer equipped with a "travelling wave" ion mobility cell, and revealed the presence of different conformational states and, remarkably, truncation and proteolytic products of high aggregating reactivity. These results suggest that different polypeptide sequences may contribute to the formation of oligomeric aggregates of heterogeneous composition and distinct biochemical properties.
authors: Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry, University of Konstanz, Konstanz, Germany.
authors: Camelia
authors: C
authors: Vlad
authors: Marius Ionut
authors: MI
authors: Iurascu
authors: Stefan
authors: S
authors: Slamnoiu
authors: Bastian
authors: B
authors: Hengerer
authors: Michael
authors: M
authors: Przybylski
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D051844:alpha-Synuclein; C078592:amyloid beta-protein (1-40)