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Calpeptin attenuated inflammation, cell death, and axonal damage in animal model of multiple sclerosis
Author(s) -
Guyton M. Kelly,
Das Arabinda,
Samantaray Supriti,
Wallace Gerald C.,
Butler Jonathan T.,
Ray Swapan K.,
Banik Naren L.
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22408
Subject(s) - calpain , multiple sclerosis , experimental autoimmune encephalomyelitis , inflammation , programmed cell death , gliosis , immunology , myelin , apoptosis , neuroprotection , microglia , neuroscience , medicine , oligodendrocyte , pharmacology , biology , central nervous system , biochemistry , enzyme
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 μg/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. © 2010 Wiley‐Liss, Inc.