Role of complement in motor neuron disease: Animal models and therapeutic potential of complement inhibitors

Woodruff, Trent R., Costantini, Kerina J., Taylor, Steve M. and Noakes, Peter G. (2008). Role of complement in motor neuron disease: Animal models and therapeutic potential of complement inhibitors. In: John D. Lambris, Current topics in complement ll. 4th Aegean Workshop on Complement Associated Diseases, Animal Models and Therapeutics, Porto Heli, Greece, (143-158). 10-17 June 2007. doi:10.1007/978-0-387-78952-1_11


Author Woodruff, Trent R.
Costantini, Kerina J.
Taylor, Steve M.
Noakes, Peter G.
Title of paper Role of complement in motor neuron disease: Animal models and therapeutic potential of complement inhibitors
Conference name 4th Aegean Workshop on Complement Associated Diseases, Animal Models and Therapeutics
Conference location Porto Heli, Greece
Conference dates 10-17 June 2007
Proceedings title Current topics in complement ll   Check publisher's open access policy
Journal name Advances in Experimental Medicine and Biology   Check publisher's open access policy
Place of Publication New York, United States
Publisher Springer New York LLC
Publication Year 2008
Year available 2008
Sub-type Fully published paper
DOI 10.1007/978-0-387-78952-1_11
Open Access Status DOI
ISBN 9780387789514
9780387789521
ISSN 0065-2598
Editor John D. Lambris
Volume 632
Start page 143
End page 158
Total pages 16
Language eng
Abstract/Summary Amyotrophic lateral sclerosis (ALS) is one of the major forms of motor neuron disease (MND), a group of degenerative disorders causing progressive motor neuron death leading to eventual paralysis and death. The pathogenesis of MND is poorly understood and may include genetic and/or environmental factors, with a common end-stage outcome. The majority of cases are sporadic, with a small percentage of familial cases identified. Mutations in the copper/zinc superoxide dismutase (SOD1) enzyme are frequent in familial ALS, and have allowed for the development of transgenic SOD1 rodent models of ALS. There has been evidence for immune system involvement in the disease, and activated components of the classical complement pathway have been observed in the serum, cerebrospinal fluid and neuronal tissue of diseased individuals. Furthermore, motor neurons and spinal cord tissue from SOD1 transgenic mice show an upregulation in C1q mRNA transcript and protein, in some cases prior to disease onset. Our laboratory has preliminary data indicating a specific pathogenic role for the activation fragment of complement C5 (C5a) in this disease. Using selective C5a receptor antagonists, we dosed SOD1 transgenic rats and observed an extension in survival and reduced motor symptoms compared to untreated rats. Collectively, these clinical and experimental findings suggest that targeting complement using specific inhibitors may represent a novel therapeutic approach to treating MND. Further experimental and clinical studies are required to validate this hypothesis. This review will summarize the clinical and experimental evidence to date implicating complement in the pathogenesis of MND.
Keyword Amyotrophic-Lateral-Sclerosis
C5A Receptor Antagonist
Cu/zn-Superoxide-Dismutase
Ischemia-Reperfusion Injury
Inflammatory-Bowel-Disease
Spinal-Cord
Rat Model
Cerebrospinal-Fluid
Transgenic Mice
Polymorphonuclear Leukocytes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Chapter 11

 
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Created: Wed, 15 Apr 2009, 19:49:54 EST by Shirley Rey on behalf of School of Biomedical Sciences