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Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders

Nature Reviews Neuroscience volume 24, pages 23–39 (2023)Cite this article

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Abstract

There is increasing appreciation that non-neuronal cells contribute to the initiation, progression and pathology of diverse neurodegenerative disorders. This Review focuses on the role of astrocytes in disorders including Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis. The important roles astrocytes have in supporting neuronal function in the healthy brain are considered, along with studies that have demonstrated how the physiological properties of astrocytes are altered in neurodegenerative disorders and may explain their contribution to neurodegeneration. Further, the question of whether in neurodegenerative disorders with specific genetic mutations these mutations directly impact on astrocyte function, and may suggest a driving role for astrocytes in disease initiation, is discussed. A summary of how astrocyte transcriptomic and proteomic signatures are altered during the progression of neurodegenerative disorders and may relate to functional changes is provided. Given the central role of astrocytes in neurodegenerative disorders, potential strategies to target these cells for future therapeutic avenues are discussed.

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Fig. 1: Astrocyte physiological alterations associated with neurodegeneration progression.
Fig. 2: Astrocyte and neuron expression of genes linked to risk of NDs.
Fig. 3: Astrocyte molecular phenotypes transition in ageing and disease.
Fig. 4: Therapeutic strategies to target astrocytes in neurodegenerative disorders.

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Acknowledgements

Work in the laboratory of N.J.A. is supported by the CZI Neurodegeneration Network. A.N.B. is supported by NINDS 1F32NS117776-01A1.

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  1. These authors contributed equally: Ashley N. Brandebura, Adrien Paumier, Tarik S. Onur.

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  1. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

    Ashley N. Brandebura, Adrien Paumier, Tarik S. Onur & Nicola J. Allen

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All authors researched data for the article and made substantial contributions to discussion of the content. A.N.B., A.P. and T.S.O. wrote the article, and N.J.A. reviewed and edited the manuscript before submission.

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Glossary

Mutations

Alterations in the sequence of DNA, which if within a coding portion of a gene can change the resulting protein product.

NG2 glia

Oligodendrocyte progenitor cells expressing NG2.

Photothrombotic stroke

Stroke model using occlusion of small cerebral vessels.

Single cell assay for transposase-accessible chromatin using sequencing

An assay that determines chromatin accessibility across the genome.

Single-nucleotide polymorphisms

Alterations to individual nucleotides in the DNA sequence.

Variants

Differences in DNA sequence between individuals.

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Brandebura, A.N., Paumier, A., Onur, T.S. et al. Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders. Nat Rev Neurosci 24, 23–39 (2023). https://doi.org/10.1038/s41583-022-00641-1

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