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Systemic inflammatory cells fight off neurodegenerative disease

Nature Reviews Neurology volume 6, pages 405–410 (2010)Cite this article

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Abstract

Treatment of Alzheimer disease or amyotrophic lateral sclerosis with anti-inflammatory drugs (to prevent disease or slow its progression) has yielded mixed results, despite evidence indicating that local cytotoxic inflammation occurs in these conditions. Here, through consideration of the importance of immune cell origin (resident versus blood-derived immune cells) and activity (pro-inflammatory versus anti-inflammatory activity) under neurodegenerative conditions, we propose a model that reconciles these seemingly inconsistent data. We suggest that systemic immune cells (CD4+ T cells and peripheral blood-derived monocytes) must be recruited to the CNS to modify potentially destructive local inflammation, and that the failure of systemic anti-inflammatory drug therapies to arrest neurodegenerative disease progression might result from drug-induced suppression of such recruitment. Thus, we propose that an appreciation of the distinctive temporal and spatial contributions of resident and systemic leukocytes to disease progression is essential for the development of effective therapeutic regimens.

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Figure 1: Immune cells in neurodegenerative conditions.
Figure 2: Model of immune responses in neurodegenerative diseases.

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Acknowledgements

M. Schwartz is in part supported by a European Research Council (http://erc.europa.eu) research grant award and by an Israel Science Foundation-Legacy grant. We thank Shelley Schwarzbaum (The Weizmann Institute of Science) for editing the manuscript and Dr Liora Cahalon (Department of Neurobiology, The Weizmann Institute of Science) for assisting in the compilation of Supplementary Table 1.

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  1. Department of Neurobiology, The Weizmann Institute of Science, Herzl Street, 76100, Rehovot, Israel

    Michal Schwartz & Ravid Shechter

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  1. Michal Schwartz
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Correspondence to Michal Schwartz.

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Supplementary information

Supplementary Table 1

Summary of the main anti-inflammatory clinical trials in Alzheimer disease and amyotrophic lateral sclerosis (DOC 126 kb)

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Schwartz, M., Shechter, R. Systemic inflammatory cells fight off neurodegenerative disease. Nat Rev Neurol 6, 405–410 (2010). https://doi.org/10.1038/nrneurol.2010.71

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