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Autoimmune Versus Oligodendrogliopathy: The Pathogenesis of Multiple Sclerosis

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS); it affect millions of patients worldwide and the number of patients is on the rise. Current treatment options are fairly limited and there is a strong unmet need for disease-targeted therapies for MS. The most widely accepted hypothesis for the pathogenesis of MS is that it is a primary autoimmune disease in which myelin-specific T cells play a central role in the progression of demyelination. According to this hypothesis, a powerful immune suppression or a reconstruction of the immune system to abrogate disease-specific leukocytes early in the development of the disease is expected to halt or even reverse the disease, since remyelination is an exceptionally efficient regenerative process in the CNS. However, recent neuropathological studies have provided evidence of primary oligodendrogliopathy as a cause of demyelination, suggesting that immune reactions may be a mere secondary event in the course of MS. On the other hand, some recent clinical trial results of new immune-suppressive treatments showed a nearly complete blockade of relapses and significant, albeit incomplete, neurological improvement. Therefore, which hypothesis—autoimmunity or oligodendrogliopathy—lights the correct path to a “cure” for MS?

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Abbreviations

ADEM:

Acute disseminating encephalomyelitis

BBB:

Blood–brain barrier

CCL:

CC chemokine ligand

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

EAE:

Experimental autoimmune encephalomyelitis

GA:

Glatiramer acetate

IFN:

Interferon

IL:

Interleukin

LT:

Lymphotoxin

MR:

Magnetic resonance

MS:

Multiple sclerosis

MTX:

Mitoxantrone

OPCs:

Oligodendrocyte precursor cells

PPMS:

Primary progressive multiple sclerosis

RRMS:

Relapsing-remitting multiple sclerosis

SAS:

Subarachnoid space

SPMS:

Secondary progressive multiple sclerosis

TNF:

Tumor necrosis factor

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Acknowledgments

Jin Nakahara is supported by the Keio University KANRINMARU Project. This work was supported by Research Grant no. 09-24 from the National Institute of Biomedical Innovation of Japan, by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Keio University Research Grants for Life Science and Medicine.

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Authors and Affiliations

  1. Department of Neurology, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Jin Nakahara & Norihiro Suzuki

  2. Department of Anatomy, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Jin Nakahara & Sadakazu Aiso

  3. Center for Integrated Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Jin Nakahara

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  1. Jin Nakahara
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  2. Sadakazu Aiso
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  3. Norihiro Suzuki
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Correspondence to Jin Nakahara.

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Nakahara, J., Aiso, S. & Suzuki, N. Autoimmune Versus Oligodendrogliopathy: The Pathogenesis of Multiple Sclerosis. Arch. Immunol. Ther. Exp. 58, 325–333 (2010). https://doi.org/10.1007/s00005-010-0094-x

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  • DOI: https://doi.org/10.1007/s00005-010-0094-x

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