Phenotypic heterogeneity of astrocytes in motor neuron disease

Abstract

Accumulating evidence has shown that astrocytes do not just support the function of neurons, but play key roles in maintaining the brain environment in health and disease. Contrary to the traditional understanding of astrocytes as static cells, reactive astrocytes possess more diverse functions and phenotypes than previously predicted. In the present focused review, we summarize the evidence showing that astrocytes are playing profound roles in the disease process of amyotrophic lateral sclerosis. Aberrantly activated astrocytes in amyotrophic lateral sclerosis rodents express microglial molecular markers and provoke toxicities to accelerate disease progression. In addition, TIR domain–containing adapter protein–inducing interferon‐β‐dependent innate immune pathway in astrocytes also has a novel function in terminating glial activation and neuroinflammation. Furthermore, heterogeneity in phenotypes and functions of astrocytes are also observed in various disease conditions, such as other neurodegenerative diseases, ischemia, aging and acute lesions in the central nervous system. Through accumulating knowledge of the phenotypic and functional diversity of astrocytes, these cells will become more attractive therapeutic targets for neurological diseases.

Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes

“…Phenotypic heterogeneity in astrocytes is also observed in the various disease conditions, such as AD, Huntington's disease, aging, brain ischemia, glioma and trauma, suggesting that the phenotypic switch is strongly associated with inflammation and tissue remodeling after damage. 7 Finally, these three review articles by experts will contribute the further understanding of neuroinflammation in diseases, leading to a better clue for future therapeutics of intractable neurodegenerative diseases and dementia.…”

“…6 Trias et al reviewed the role of astrocytes in ALS, an adult neurodegenerative disease characterized by selective death of motor neurons. 7 By the use of selective gene ablation of ALS-causing mutant genes from an ALS mouse model, they showed the active roles of astrocytes in disease progression. 8 Furthermore, they identified phenotypic heterogeneity in reactive astrocytes in ALS.…”

Astrocytes: News about Brain Health and Diseases

“…At present, the research is clear that the properties of astrocytes, widespread in young age, are also maintained in mature mice and rats if in good health [ 12 , 13 , 14 , 15 ]. During aging, however, many changes and alterations have been reported [ 16 , 17 , 18 , 19 ]. The interactions of heterogeneous astrocytes with neurons are critical for many key events of brain development and function, including the formation and function of synapses, their release and reuptake of transmitters, the production of trophic and toxic factors, and the control of neuronal survival [ 12 , 13 ] ( Figure 1 ).…”

“…The interactions of heterogeneous astrocytes with neurons are critical for many key events of brain development and function, including the formation and function of synapses, their release and reuptake of transmitters, the production of trophic and toxic factors, and the control of neuronal survival [ 12 , 13 ] ( Figure 1 ). These interactions are due to the molecular properties of astrocytes, with differences in the expression of distinct genes (a) at various stages of their functions; (b) at various regions of the brain [ 20 ]; (c) in neuronal circuit regulation [ 21 ], and (d) also in the course of their pathologies [ 16 , 17 , 18 , 19 ].…”

Neuroinflammation in dementia and neurodegeneration

“…Trias et al. reviewed the role of astrocytes in ALS, an adult neurodegenerative disease characterized by selective death of motor neurons . By the use of selective gene ablation of ALS‐causing mutant genes from an ALS mouse model, they showed the active roles of astrocytes in disease progression .…”