Ion mobility-mass spectrometry and orthogonal gas-phase techniques to study amyloid formation and inhibition.
Amyloidogenic peptide oligomers are responsible for a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Due to their dynamic, polydisperse, and polymorphic nature, these oligomers are very challenging to characterize using traditional condensed-phase methods. In the last decade, ion mobility-mass spectrometry (IM-MS) and related gas-phase techniques have emerged as a powerful alternative to disentangle the structure and assembly characteristics of amyloid forming systems. This review highlights recent advances in which IM-MS was used to characterize amyloid oligomers and their underlying assembly pathway. In addition, we summarize recent studies in which IM-MS was used to size- and mass-select species for a further spectroscopic investigation and outline the potential of IM-MS as a tool for the screening of amyloid inhibitors.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany; Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
Waldemar
W
Hoffmann
Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
Gert
G
von Helden
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany; Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany. Electronic address: kevin.pagel@fu-berlin.de.
Kevin
K
Pagel
D000682:Amyloid / Q000737:chemistry*; D055808:Drug Discovery; D005740:Gases / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D066329:Protein Aggregates / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects
D000682:Amyloid; D005740:Gases; D066329:Protein Aggregates