Evidence for a growing involvement of glia in amyotrophic lateral sclerosis

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating disease that is characterized by the loss of muscle control due to the degeneration of motor neurons in the brain and the spinal cord. Although it's the motor neurons that die in ALS, non‐neuronal cells are also involved in disease pathogenesis. Glial cells, including microglia, astrocytes, and oligodendrocytes, surround and support motor neurons, and pathological changes of glia have been unequivocally linked to the onset and progression of ALS. Microglia and astrocyte activation in particular are considered a hallmark feature and are directly associated with ALS neurodegeneration. Nevertheless, the precise contributions of glial cells to disease pathogenesis in ALS and neurodegeneration remain elusive. One reason is that the evolving contribution of glial cells is likely to change during the course of the disease and therefore is often difficult to track longitudinally. In this chapter, we will summarize and review the current evidence for the effects of astrocytes, microglia, and oligodendrocytes on motor neuron survival in ALS and discuss their relevance for the different disease subtypes. We also discuss how modulating neuron–glia interactions might have important therapeutic implications by highlighting some of their fundamental regulatory functions in ALS pathogenesis. We review the popular term neuroinflammation in relation to ALS. A deeper understanding of how we can preserve the protective function of glial cells while suppressing their potentially toxic behavior might offer new avenues for combinatorial therapies that help to delay or ultimately stop the rapid progression of neurodegeneration.
Original languageEnglish
Title of host publicationSpectrums of amyotrophic lateral sclerosis
Subtitle of host publicationheterogeneity, pathogenesis and therapeutic directions
EditorsChristopher A. Shaw, Jessica R. Morrice
Place of PublicationHoboken, NJ
PublisherJohn Wiley & Sons
Chapter7
Pages123-142
Number of pages20
ISBN (Electronic)9781119745518
ISBN (Print)9781119745495
DOIs
Publication statusPublished - 27 Apr 2021

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