Detection of Proteolytic Signatures for Parkinson's Disease

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.

KEYWORDS:

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

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/fnl.16.3

Financial & competing interests disclosure

This study was supported by the Michael J Fox Foundation and the Danish Agency for Science, Technology and Innovation (Innovation Consortium CureND). Bispebjerg Movement Disorders Biobank is supported by The John and Birthe Meyer Foundation and the ANT Foundation. MR Larson was funded by the Lundbeck Foundation (Junior Group Leader Fellowship). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

The authors acknowledge Sami Mahrus and David Wildes for skilled assistance in optimizing experimental conditions for subtiligase-mediated biotinylation of protein N-termini.

Additional information

Funding

This study was supported by the Michael J Fox Foundation and the Danish Agency for Science, Technology and Innovation (Innovation Consortium CureND). Bispebjerg Movement Disorders Biobank is supported by The John and Birthe Meyer Foundation and the ANT Foundation. MR Larson was funded by the Lundbeck Foundation (Junior Group Leader Fellowship). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.