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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration

Isobel A. Scarisbrick1 / Rachel Linbo2 / Alexander G. Vandell3 / Mark Keegan4 / Sachiko I. Blaber5 / Michael Blaber6 / Diane Sneve7 / Claudia F. Lucchinetti8 / Moses Rodriguez9 / Eleftherios P. Diamandis10

1Program for Molecular Neuroscience, Mayo Clinic College of Medicine, Rochester, MN 55905, USA and Departments of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Rochester, MN 55905, USA and Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

2Departments of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

3Program for Molecular Neuroscience, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

4Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

5Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306-4300, USA

6Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306-4300, USA

7Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

8Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

9Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

10Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto M5G 1X5, Ontario, Canada

Corresponding author

Citation Information: Biological Chemistry. Volume 389, Issue 6, Pages 739–745, ISSN (Online) 14374315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2008.085, May 2008

Publication History

Received:
2007-11-30
Accepted:
2008-02-27
Published Online:
2008-05-15

Abstract

Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

Keywords: axon injury; kallikrein; prognosis; serine protease

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