Document Detail


Calpeptin attenuated inflammation, cell death, and axonal damage in animal model of multiple sclerosis.
MedLine Citation:
PMID:  20623621     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Experimental autoimmune encephalomyelitis (EAE) is an animal model for studying multiple sclerosis (MS). Calpain has been implicated in many inflammatory and neurodegenerative events that lead to disability in EAE and MS. Thus, treating EAE animals with calpain inhibitors may block these events and ameliorate disability. To test this hypothesis, acute EAE Lewis rats were treated dose dependently with the calpain inhibitor calpeptin (50-250 microg/kg). Calpain activity, gliosis, loss of myelin, and axonal damage were attenuated by calpeptin therapy, leading to improved clinical scores. Neuronal and oligodendrocyte death were also decreased, with down-regulation of proapoptotic proteins, suggesting that decreases in cell death were due to decreases in the expression or activity of proapoptotic proteins. These results indicate that calpain inhibition may offer a novel therapeutic avenue for treating EAE and MS.
Authors:
M Kelly Guyton; Arabinda Das; Supriti Samantaray; Gerald C Wallace; Jonathan T Butler; Swapan K Ray; Naren L Banik
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  88     ISSN:  1097-4547     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-13     Completed Date:  2010-10-20     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2398-408     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
Affiliation:
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Axons / drug effects*,  pathology*
Blotting, Western
Calpain / antagonists & inhibitors
Cell Death / drug effects*
Cysteine Proteinase Inhibitors / pharmacology*
Dipeptides / pharmacology*
Down-Regulation / physiology
Encephalomyelitis, Autoimmune, Experimental / drug therapy*,  pathology*
Fluorescent Antibody Technique
Gliosis / chemically induced,  pathology
In Situ Nick-End Labeling
Inflammation / pathology,  prevention & control*
Male
Multiple Sclerosis / drug therapy*,  pathology*
Nerve Tissue Proteins / biosynthesis
Oligodendroglia / pathology
Rats
Rats, Inbred Lew
Spinal Cord / pathology
Tissue Embedding
Grant Support
ID/Acronym/Agency:
C06 RR015455-01A1/RR/NCRR NIH HHS; C06RR-015455/RR/NCRR NIH HHS; CA-91460/CA/NCI NIH HHS; NS-38146/NS/NINDS NIH HHS; NS-41088/NS/NINDS NIH HHS; NS-56176/NS/NINDS NIH HHS; NS-57811/NS/NINDS NIH HHS; R01 NS038146-05/NS/NINDS NIH HHS; R01 NS041088-07/NS/NINDS NIH HHS; R01 NS056176-05/NS/NINDS NIH HHS; R01 NS057811-04/NS/NINDS NIH HHS; R01 NS065456-03/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Cysteine Proteinase Inhibitors; 0/Dipeptides; 0/Nerve Tissue Proteins; 117591-20-5/calpeptin; EC 3.4.22.-/Calpain
Comments/Corrections

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