Calpeptin attenuated inflammation, cell death, and axonal damage in animal model of multiple sclerosis.
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.
Guyton
M Kelly
MK
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Das
Arabinda
A
Samantaray
Supriti
S
Wallace
Gerald C
GC
Butler
Jonathan T
JT
Ray
Swapan K
SK
Banik
Naren L
NL
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology*; D015153:Blotting, Western; D002154:Calpain / Q000037:antagonists & inhibitors; D016923:Cell Death / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009836:Oligodendroglia / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology; D016610:Tissue Embedding
D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D009419:Nerve Tissue Proteins; C071482:calpeptin; D002154:Calpain