Document Detail

Neuroprotective function of cellular prion protein in a mouse model of amyotrophic lateral sclerosis.
MedLine Citation:
PMID:  20075202     Owner:  NLM     Status:  MEDLINE    
Transgenic mice expressing human mutated superoxide dismutase 1 (SOD1) linked to familial forms of amyotrophic lateral sclerosis are frequently used as a disease model. We used the SOD1G93A mouse in a cross-breeding strategy to study the function of physiological prion protein (Prp). SOD1G93APrp-/- mice exhibited a significantly reduced life span, and an earlier onset and accelerated progression of disease, as compared with SOD1G93APrp+/+ mice. Additionally, during disease progression, SOD1G93APrp-/- mice showed impaired rotarod performance, lower body weight, and reduced muscle strength. Histologically, SOD1G93APrp-/- mice showed reduced numbers of spinal cord motor neurons and extended areas occupied by large vacuoles early in the course of the disease. Analysis of spinal cord homogenates revealed no differences in SOD1 activity. Using an unbiased proteomic approach, a marked reduction of glial fibrillary acidic protein and enhanced levels of collapsing response mediator protein 2 and creatine kinase were detected in SOD1G93APrp-/- versus SOD1G93A mice. In the course of disease, Bcl-2 decreases, nuclear factor-kappaB increases, and Akt is activated, but these changes were largely unaffected by Prp expression. Exclusively in double-transgenic mice, we detected a significant increase in extracellular signal-regulated kinase 2 activation at clinical onset. We propose that Prp has a beneficial role in the SOD1G93A amyotrophic lateral sclerosis mouse model by influencing neuronal and/or glial factors involved in antioxidative defense, rather than anti-apoptotic signaling.
Petra Steinacker; Andreas Hawlik; Stefan Lehnert; Olaf Jahn; Stephen Meier; Evamaria Görz; Kerstin E Braunstein; Marija Krzovska; Birgit Schwalenstöcker; Sarah Jesse; Christian Pröpper; Tobias Böckers; Albert Ludolph; Markus Otto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-14
Journal Detail:
Title:  The American journal of pathology     Volume:  176     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-10     Completed Date:  2010-06-07     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1409-20     Citation Subset:  AIM; IM    
Department of Neurology, University of Ulm, Steinhovelstr.1, 89075 Ulm, Germany.
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MeSH Terms
Amyotrophic Lateral Sclerosis / enzymology,  metabolism*,  pathology
Brain / enzymology,  pathology
Cell Count
DNA / metabolism
Disease Models, Animal
Disease Progression
Enzyme Activation
Glial Fibrillary Acidic Protein / metabolism
Mice, Transgenic
Mitogen-Activated Protein Kinase 1 / metabolism
Motor Neurons / pathology
Neuroprotective Agents / metabolism*
Prions / metabolism*
Spinal Cord / enzymology,  pathology
Superoxide Dismutase / genetics
Survival Analysis
Transgenes / genetics
Vacuoles / metabolism
Reg. No./Substance:
0/Glial Fibrillary Acidic Protein; 0/Neuroprotective Agents; 0/Prions; 0/Prnp protein, mouse; 9007-49-2/DNA; EC 1.15.1.-/superoxide dismutase 1; EC Dismutase; EC Protein Kinase 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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