Detection of proteolytic signatures for Parkinson's disease

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DOI

  • Peter Lüttge Jordal
  • ,
  • Thomas F. Dyrlund
  • ,
  • Kristian Winge, University of Copenhagen
  • ,
  • Martin R. Larsen, Department of Biochemistry and Molecular Biology, University of Southern Denmark, University of Southern Denmark
  • ,
  • Erik H. Danielsen
  • James A. Wells, University of California, San Francisco
  • ,
  • Daniel E. Otzen
  • Jan J. Enghild

Aim: To investigate if idiopathic Parkinson's disease (IPD) is associated with distinct proteolytic signatures relative to non-neurodegenerative controls (NND) and patients with multiple system atrophy (MSA). Materials & methods: A subtiligase-based N-terminomics screening method was exploited for semiquantitative comparison of protein N-termini in cerebrospinal fluid for pooled samples of IPD (n = 6) and NND (n = 8) individuals. Subsequently, targeted selected reaction monitoring mass spectrometry measured the relative concentration of the proteolytic signature peptides in individual IPD (n = 22), NND (n = 11) and MSA (n = 18) samples. Results: The discovery screen detected 300 N-termini for 156 proteins. Selected reaction monitoring analysis revealed that two of these peptides differentiate IPD from NND while three peptides differentiate IPD from MSA. Conclusion: IPD is associated with distinct proteolytic signatures.

Original languageEnglish
JournalFuture Neurology
Volume11
Issue1
Pages (from-to)15-32
Number of pages18
ISSN1479-6708
DOIs
Publication statusPublished - 1 Feb 2016

    Research areas

  • cerebrospinal fluid, N-terminomics, Parkinson's disease

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