The Structure of Lewy Bodies by Scanning X-ray Diffraction and Infrared Spectromicroscopy

A crucial step in the etiopathology of Parkinson’s disease (PD) is the development of protein aggregates in the brain, which are known as Lewy Bodies (LB) and contain the protein α-synuclein as a major component. We have recently shown that LBs can form in a minimal system, based on cell culture. The current proposal now aims at a comparative structural and spectromicroscopic study of LBs in two different systems: (a) postmortem-brains of PD patients, (b) LBs in a minimal system (cell culture, controlled over-expression of the protein alpha- synuclein). We will use scanning nano-diffraction as well as synchrotron radiation-based infrared spectro-microscopy (SR-FTIR). A particular target of the study is the protein secondary conformation in different LB systems. Using the minimal system, we will monitor beta-sheet content as a function of incubation time, as well as other structural and spectromicroscopic parameters.