Calpeptin attenuated inflammation, cell death, and axonal damage in animal model of multiple sclerosis.

Abstract	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 4th, Jonathan T Butler, Swapan K Ray, Naren L Banik
Journal	Journal of neuroscience research (J Neurosci Res) Vol. 88 Issue 11 Pg. 2398-408 (Aug 15 2010) ISSN: 1097-4547 [Electronic] United States
PMID	20623621 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright	(c) 2010 Wiley-Liss, Inc.
Chemical References	Cysteine Proteinase Inhibitors Dipeptides Nerve Tissue Proteins calpeptin Calpain
Topics	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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!