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Experimental Autoimmune Encephalomyelitis in the Pathogenesis of Optic Neuritis: Is Calpain Involved?

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Multiple sclerosis (MS) is a debilitating, autoimmune disease of the central nervous system (CNS) that attacks 1 in every 1,000 Americans each year. Patients suffer clinical symptoms including fatigue, paralysis, and visual dysfunction as a result of demyelination and degeneration of axons and neurons. Since visual dysfunction results from pathophysiological changes in the optic nerve, the animal model of MS, experimental autoimmune encephalomyelitis (EAE), is also used as a tool to study optic neuritis (ON). Previous reports have indicated that the calcium (Ca2+)-activated neutral protease calpain may be involved in multiple pathways leading to the development of EAE and EAE-induced ON. These mechanisms include T cell activation and migration, demyelination, and apoptosis of neurons and glial cells. Upregulation of calpain in MS patients further supports this hypothesis. The purpose of this chapter is to discuss and summarize literature involving calpain in EAE and MS, with special emphasis on how calpain may be involved in the development of ON in EAE animals and MS patients.

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Abbreviations

AIF:

apoptosis-inducing factor

Ca2+ :

calcium

CFA:

complete Freund’s adjuvant

CNS:

central nervous system

CSF:

cerebrospinal fluid

de-NFP:

dephosphorylation of NFP

EAE:

experimental autoimmune encephalomyelitis

ER:

endoplasmic reticulum

IFN-γ:

interferon-gamma

IL:

interleukin

IV:

intravenous

LFA:

leukocyte function-associated antigen

MAG:

myelin-associated glycoprotein

MBP:

myelin basic protein

MCP-1:

monocyte chemotactic protein-1

MHC II:

major histocompatibility complex II

MOG:

myelin oligodendrocyte glycoprotein

MS:

multiple sclerosis

NFκB:

nuclear factor kappa-B

NFP:

neurofilament protein

ON:

optic neuritis

PBMCs:

peripheral blood mononuclear cells

PKC:

protein kinase C

PLP:

proteolipid protein

R/R:

relapsing/remitting

RGCs:

retinal ganglion cells

RRMS:

relapsing remitting MS

SPMS:

secondary progressive MS

STAT:

signal transducer and activator of signaling

TBI:

traumatic brain injury

TCR:

T cell receptor

TNF-α:

tumor necrosis factor-alpha

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Acknowledgments

This work was supported in part by the R01 grants (CA-91460, NS-31622, NS-38146, NS-41088, NS-45967, NS-56176, and NS-57811) from the National Institutes of Health and Spinal Cord Injury Research Foundation grants (SCIRF-0803, SCIRF-1205, and SCIRF-607) from the State of South Carolina.

Authors
  1. M. K. Guyton
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  2. A. W. Smith
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  3. S. K. Ray
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  4. N. L. Banik
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 29425, 96 Jonathan Lucas Street, Suite 309, Charleston, SC, USA

    Naren Banik

  3. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 29209, 6439 Garners Ferry Road Building 2, Room C11, Columbia, SC, USA

    Swapan K. Ray

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Guyton, M.K., Smith, A.W., Ray, S.K., Banik, N.L. (2009). Experimental Autoimmune Encephalomyelitis in the Pathogenesis of Optic Neuritis: Is Calpain Involved?. In: Lajtha, A., Banik, N., Ray, S.K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30375-8_22

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