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  From classic to spontaneous and humanized models of multiple sclerosis: Impact on understanding pathogenesis and drug development

Ben-Nun, A., Kaushansky, N., Kawakami, N., Krishnamoorthy, G., Berer, K., Liblau, R., et al. (2014). From classic to spontaneous and humanized models of multiple sclerosis: Impact on understanding pathogenesis and drug development. JOURNAL OF AUTOIMMUNITY, 54, 33-50. doi:10.1016/j.jaut.2014.06.004.

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 Creators:
Ben-Nun, Avraham1, Author
Kaushansky, Nathali1, Author
Kawakami, Naoto2, Author              
Krishnamoorthy, Gurumoorthy2, Author              
Berer, Kerstin2, Author              
Liblau, Roland1, Author
Hohlfeld, Reinhard1, Author
Wekerle, Hartmut2, Author              
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1external, ou_persistent22              
2Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

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Free keywords: EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; T-CELL-RECEPTOR; BASIC-PROTEIN PEPTIDE; ANTIGEN-PRESENTING CELLS; REDUCES RELAPSE RATE; CD8(+) T; B-CELLSExperimental autoimmune encephlalomyelitis (EAE); Spontaneous EAE models; Humanized EAE models; Multiple sclerosis (MS); HLA-II transgenic mice; Antigen-based immune-specific therapy;
 Abstract: Multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), presents as a complex disease with variable clinical and pathological manifestations, involving different pathogenic pathways. Animal models, particularly experimental autoimmune encephalomyelitis (EAE), have been key to deciphering the pathophysiology of MS, although no single model can recapitulate the complexity and diversity of MS, or can, to date, integrate the diverse pathogenic pathways. Since the first EAE model was introduced decades ago, multiple classic (induced), spontaneous, and humanized EAE models have been developed, each recapitulating particular aspects of MS pathogenesis. The advances in technologies of genetic ablation and transgenesis in mice of C57BL/6J background and the development of myelinoligodendrocyte glycoprotein (MOG)-induced EAE in C57BL/6J mice yielded several spontaneous and humanized EAE models, and resulted in a plethora of EAE models in which the role of specific genes or cell populations could be precisely interrogated, towards modeling specific pathways of MS pathogenesis/regulation in MS. Collectively, the numerous studies on the different EAE models contributed immensely to our basic understanding of cellular and molecular pathways in MS pathogenesis as well as to the development of therapeutic agents: several drugs available today as disease modifying treatments were developed from direct studies on EAE models, and many others were tested or validated in EAE. In this review, we discuss the contribution of major classic, spontaneous, and humanized EAE models to our understanding of MS pathophysiology and to insights leading to devising current and future therapies for this disease. (C) 2014 Elsevier Ltd. All rights reserved.

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Language(s): eng - English
 Dates: 2014-11
 Publication Status: Published in print
 Pages: 18
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: JOURNAL OF AUTOIMMUNITY
Source Genre: Journal
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Publ. Info: 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Pages: - Volume / Issue: 54 Sequence Number: - Start / End Page: 33 - 50 Identifier: ISSN: 0896-8411