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No quiet surrender: molecular guardians in multiple sclerosis brain
Lawrence Steinman
Lawrence Steinman
Published April 1, 2015
Citation Information: J Clin Invest. 2015;125(4):1371-1378. https://doi.org/10.1172/JCI74255.
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Review

No quiet surrender: molecular guardians in multiple sclerosis brain

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Abstract

The brain under immunological attack does not surrender quietly. Investigation of brain lesions in multiple sclerosis (MS) reveals a coordinated molecular response involving various proteins and small molecules ranging from heat shock proteins to small lipids, neurotransmitters, and even gases, which provide protection and foster repair. Reduction of inflammation serves as a necessary prerequisite for effective recovery and regeneration. Remarkably, many lesion-resident molecules activate pathways leading to both suppression of inflammation and promotion of repair mechanisms. These guardian molecules and their corresponding physiologic pathways could potentially be exploited to silence inflammation and repair the injured and degenerating brain and spinal cord in both relapsing-remitting and progressive forms of MS and may be beneficial in other neurologic and psychiatric conditions.

Authors

Lawrence Steinman

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Figure 1

Natalizumab blocks lymphocyte homing in MS.

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Natalizumab blocks lymphocyte homing in MS.
(A) α4 integrin binds to vas...
(A) α4 integrin binds to vascular cell adhesion molecule 1 (VCAM1) on inflamed brain endothelium. This interaction gives lymphocytes access to the CNS. The presence of immune cells in the brain is a prominent feature of MS. (B) Natalizumab, a humanized antibody against α4 integrin, blocks binding of lymphocytes to VCAM on inflamed brain endothelium, thereby preventing lymphocyte entry into the CNS. Reproduced with permission from ref. 36 (Used with permission: © 2012 Steinman. Journal of Cell Biology. 199:413–416. doi: 10.1083/jcb.201207175).

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