Protein crosslinks are a defining feature of amyloid plaques and Lewy bodies, which are associated with neurodegenerative diseases. Although most research has centred on a few well-established and easily detectable types of crosslink, mounting evidence suggests that these account for only a small proportion of the total complement. This indicates that a wide variety of other crosslinks are present in proteins associated with neuropathology. To identify novel types of crosslink, there is an urgent need to develop improved methods to characterise, quantify and map crosslinks in a holistic and unbiased manner, rather than studying them one at a time.
This project aims to develop an agnostic (i.e. mode-independen) mass spectrometry approach for the unbiased and comprehensive detection of protein crosslinks. As a proof of concept, the focus will be on α-synuclein, the main protein associated with Parkinson’s disease. However, the workflow should be widely applicable to protein crosslink analysis in a variety of scientific disciplines and industries.
For further information about this HALRIC pilot project, please contact:
Per Mårten Hägglund
University of Copenhagen
pmh@sund.ku.dk