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01-02-2020 | Multiple Sclerosis | Original Paper

The active contribution of OPCs to neuroinflammation is mediated by LRP1

Authors: Anthony Fernández-Castañeda, Megan S. Chappell, Dorian A Rosen, Scott M. Seki, Rebecca M. Beiter, David M. Johanson, Delaney Liskey, Emily Farber, Suna Onengut-Gumuscu, Christopher C. Overall, Jeffrey L. Dupree, Alban Gaultier

Published in: Acta Neuropathologica | Issue 2/2020

Abstract

Oligodendrocyte progenitor cells (OPCs) account for about 5% of total brain and spinal cord cells, giving rise to myelinating oligodendrocytes that provide electrical insulation to neurons of the CNS. OPCs have also recently been shown to regulate inflammatory responses and glial scar formation, suggesting functions that extend beyond myelination. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifaceted phagocytic receptor that is highly expressed in several CNS cell types, including OPCs. Here, we have generated an oligodendroglia-specific knockout of LRP1, which presents with normal myelin development, but is associated with better outcomes in two animal models of demyelination (EAE and cuprizone). At a mechanistic level, LRP1 did not directly affect OPC differentiation into mature oligodendrocytes. Instead, animals lacking LRP1 in OPCs in the demyelinating CNS were characterized by a robust dampening of inflammation. In particular, LRP1-deficient OPCs presented with impaired antigen cross-presentation machinery, suggesting a failure to propagate the inflammatory response and thus promoting faster myelin repair and neuroprotection. Our study places OPCs as major regulators of neuroinflammation in an LRP1-dependent fashion.

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Title: The active contribution of OPCs to neuroinflammation is mediated by LRP1
Authors: Anthony Fernández-Castañeda
Megan S. Chappell
Dorian A Rosen
Scott M. Seki
Rebecca M. Beiter
David M. Johanson
Delaney Liskey
Emily Farber
Suna Onengut-Gumuscu
Christopher C. Overall
Jeffrey L. Dupree
Alban Gaultier
Publication date: 01-02-2020
Publisher: Springer Berlin Heidelberg
Keyword: Multiple Sclerosis
Published in: Acta Neuropathologica / Issue 2/2020
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-02073-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The active contribution of OPCs to neuroinflammation is mediated by LRP1

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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