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Review
. 2020 Dec 1;143(12):3526-3539.
doi: 10.1093/brain/awaa309.

The microglial component of amyotrophic lateral sclerosis

Benjamin E Clarke  1   2 , Rickie Patani  1   2
Affiliations
Review

The microglial component of amyotrophic lateral sclerosis

Benjamin E Clarke et al. Brain. .

Abstract

Microglia are the primary immune cells of the CNS, carrying out key homeostatic roles and undergoing context-dependent and temporally regulated changes in response to injury and neurodegenerative diseases. Microglia have been implicated in playing a role in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by extensive motor neuron loss leading to paralysis and premature death. However, as the pathomechansims of ALS are increasingly recognized to involve a multitude of different cell types, it has been difficult to delineate the specific contribution of microglia to disease. Here, we review the literature of microglial involvement in ALS and discuss the evidence for the neurotoxic and neuroprotective pathways that have been attributed to microglia in this disease. We also discuss accumulating evidence for spatiotemporal regulation of microglial activation in this context. A deeper understanding of the role of microglia in the 'cellular phase' of ALS is crucial in the development of mechanistically rationalized therapies.

Keywords: ALS; ageing; astrocyte; microglia.

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Figures

Figure 1
Figure 1
Multiple cell types affect microglial responses in ALS. Both astrocytes and peripheral immune cells that infiltrate the CNS during ALS disease progression can affect microglial responses, resulting in an overall protective or toxic microglial phenotype. Changes in cellular composition, ageing and factors released from dying cells are also likely to affect the microglial phenotype in ALS. Components of this figure were created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License.
Figure 2
Figure 2
Several factors have been either directly or indirectly implicated in affecting microglial activation and disease progression in ALS. Certain receptors including xCT and P2X7 have been linked to both neuroprotection and neurotoxicity depending on the stage of disease progression. Components of this figure were created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License.
See this image and copyright information in PMC

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