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Mechanisms of Disease: astrocytes in neurodegenerative disease

Nature Clinical Practice Neurology volume 2, pages 679–689 (2006)Cite this article

Abstract

The term neurodegenerative disease refers to the principal pathology associated with disorders such as amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease and Parkinson's disease, and it is presumed that neurodegeneration results in the clinical findings seen in patients with these diseases. Decades of pathological and physiological studies have focused on neuronal abnormalities in these disorders, but it is becoming increasingly evident that astrocytes are also important players in these and other neurological disorders. Our understanding of the normative biology of astrocytes has been aided by the development of animal models in which astrocyte-specific proteins and pathways have been manipulated, and mouse models of neurodegenerative diseases have also revealed astrocyte-specific pathologies that contribute to neurodegeneration. These models have led to the development of targeted therapies for pathways in which astrocytes participate, and this research should ultimately influence the clinical treatment of neurodegenerative disorders.

Key Points

  • Astrocytes perform critical roles in amino acid, nutrient and ion metabolism in the brain, coupling of neuronal activity and cerebral blood flow, and modulation of excitatory synaptic transmission

  • Transgenic and knockout mouse models of astrocyte-specific proteins have demonstrated that astrocytes play a role in both neuroprotection and neurodegeneration, particularly following an insult

  • Selective expression of mutant proteins associated with neurodegenerative diseases in astrocytes is sufficient to cause neuronal damage

  • Mutations in the astrocyte-specific intermediate filament protein glial fibrillary acidic protein is associated with the neurodegenerative disorder Alexander disease

  • Astrocytes might be particularly attractive—and underappreciated—targets for neurodegenerative disease therapeutics

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Figure 1: Normal functions of astrocytes.
Figure 2: Potential astrocyte dysfunction in neurodegenerative diseases.

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Author notes

  1. NJ Maragakis is an assistant professor of neurology, and JD Rothstein is Professor of Neurology and Neuroscience and a member of the Program in Cellular and Molecular Medicine, both at the Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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  1. Nicholas J Maragakis
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  2. Jeffrey D Rothstein
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Maragakis, N., Rothstein, J. Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Rev Neurol 2, 679–689 (2006). https://doi.org/10.1038/ncpneuro0355

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