Elsevier

Neuroscience Research

Volume 126, January 2018, Pages 31-38
Neuroscience Research

Review article
The multi-dimensional roles of astrocytes in ALS

https://doi.org/10.1016/j.neures.2017.09.011Get rights and content
Under a Creative Commons license
open access

Highlights

  • Neurodegeneration in ALS is partly mediated by non-cell autonomous mechanism.

  • Astrocytes in ALS lose neuroprotective property and acquire toxic phenotypes.

  • Astrocytes are a viable therapeutic target for ALS.

Abstract

Despite significant progress in understanding the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, the precise and comprehensive pathomechanisms remain largely unknown. In addition to motor neuron involvement, recent studies using cellular and animal models of ALS indicate that there is a complex interplay between motor neurons and neighboring non-neuronal cells, such as astrocytes, in non-cell autonomous neurodegeneration. Astrocytes are key homeostatic cells that play numerous supportive roles in maintaining the brain environment. In neurodegenerative diseases such as ALS, astrocytes change their shape and molecular expression patterns and are referred to as reactive or activated astrocytes. Reactive astrocytes in ALS lose their beneficial functions and gain detrimental roles. In addition, interactions between motor neurons and astrocytes are impaired in ALS. In this review, we summarize growing evidence that astrocytes are critically involved in the survival and demise of motor neurons through several key molecules and cascades in astrocytes in both sporadic and inherited ALS. These observations strongly suggest that astrocytes have multi-dimensional roles in disease and are a viable therapeutic target for ALS.

Keywords

Astrocyte
Neuroinflammation
ALS
TDP-43
SOD1

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