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Open Access 01-09-2014 | Review

The role of microglia in human disease: therapeutic tool or target?

Authors: Nathalie Cartier, Coral-Ann Lewis, Regan Zhang, Fabio M. V. Rossi

Published in: Acta Neuropathologica | Issue 3/2014

Abstract

Microglia have long been the focus of much attention due to their strong proliferative response (microgliosis) to essentially any kind of damage to the CNS. More recently, we reached the realization that these cells play specific roles in determining progression and outcomes of essentially all CNS disease. Thus, microglia has ceased to be viewed as an accessory to underlying pathologies and has now taken center stage as a therapeutic target. Here, we review how our understanding of microglia’s involvement in promoting or limiting the pathogenesis of diseases such as amyotrophic lateral sclerosis, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, X-linked adrenoleukodystrophy (X-ALD) and lysosomal storage diseases (LSD) has changed over time. While strategies to suppress the deleterious and promote the virtuous functions of microglia will undoubtedly be forthcoming, replacement of these cells has already proven its usefulness in a clinical setting. Over the past few years, we have reached the realization that microglia have a developmental origin that is distinct from that of bone marrow-derived myelomonocytic cells. Nevertheless, microglia can be replaced, in specific situations, by the progeny of hematopoietic stem cells (HSCs), pointing to a strategy to engineer the CNS environment through the transplantation of modified HSCs. Thus, microglia replacement has been successfully exploited to deliver therapeutics to the CNS in human diseases such as X-ALD and LSD. With this outlook in mind, we will discuss the evidence existing so far for microglial involvement in the pathogenesis and the therapy of specific CNS disease.

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Title: The role of microglia in human disease: therapeutic tool or target?
Authors: Nathalie Cartier
Coral-Ann Lewis
Regan Zhang
Fabio M. V. Rossi
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 3/2014
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-014-1330-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The role of microglia in human disease: therapeutic tool or target?

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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