Detection of proteolytic signatures for Parkinson's disease

Author:

Jordal Peter Lüttge123,Dyrlund Thomas F2,Winge Kristian4,Larsen Martin R5,Danielsen Erik H6,Wells James A7,Otzen Daniel E23,Enghild Jan J23

Affiliation:

1. Section for Medical Biotechnology, Danish Technological Institute, 8000 Aarhus C, Denmark

2. Department of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus C, Denmark

3. iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark

4. Bispebjerg Movement Disorders Biobank, Department of Neurology, Bispebjerg University Hospital, 2400, Copenhagen NV, Denmark

5. Department of Biochemistry & Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark

6. Department of Neurology, Aarhus University Hospital, 8000 Aarhus C, Denmark

7. Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Neurology (clinical),Neurology

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