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Revisiting the critical roles of reactive astrocytes in neurodegeneration

Molecular Psychiatry volume 28, pages 2697–2706 (2023)Cite this article

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Abstract

Astrocytes, an integral component of the central nervous system (CNS), contribute to the maintenance of physiological homeostasis through their roles in synaptic function, K+ buffering, blood-brain barrier (BBB) maintenance, and neuronal metabolism. Reactive astrocytes refer to astrocytes undergoing morphological, molecular and functional remodelling in response to pathological stimuli. The activation and differentiation of astrocytes are implicated in the pathogenesis of multiple neurodegenerative diseases. However, there are still controversies regarding their subset identification, function and nomenclature in neurodegeneration. In this review, we revisit the multidimensional roles of reactive astrocytes in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Furthermore, we propose a precise linkage between astrocyte subsets and their functions based on single-cell sequencing analyses.

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Fig. 1: Common astrocyte-related pathogenesis of AD.
Fig. 2: Double-edge functions of astrocytes in neuroinflammation.
Fig. 3: SnRNA-seq analysis of astrocytes from AD, PD and MS.

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Acknowledgements

We thank the Medical Subcenter of HUST Analytical & Testing Centerin data acquisition. Thanks for the technical support by the Huazhong University of Science & Technology Analytical & Testing center, Medical sub-center. This study is supported by National Key Research and Development Program of China (Grant No. 2019YFE0121200), and National Natural Science Foundation of China (82030032, 82261138555, 32070960, 81871108, 31721002, 81829002), Top-Notch Young Talents Program of China of 2014 to LQZ, the Hubei Provincial Natural Science Foundation (2022CFA004 to LQZ and 2020CFB811 to YS).

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  1. These authors contributed equally: Kang Qian, Xiaobing Jiang, Zhi-Qiang Liu.

Authors and Affiliations

  1. Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Kang Qian, Zhi-Qiang Liu, Juan Zhang & Ling-Qiang Zhu

  2. Department of Neurosurgery, Union Hospital, Huazhong University of Science and Technology, Jiefang Avenue No. 1277, 430022, Wuhan, China

    Kang Qian, Xiaobing Jiang & Peng Fu

  3. Department of Neurology, Union Hospital, Huazhong University of Science and Technology, Jiefang Avenue No. 1277, 430022, Wuhan, China

    Ying Su

  4. Biophysics Department, Biological Faculty, Moscow State University, Moscow, Russia

    Nadezda A. Brazhe

  5. Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Dan Liu

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Contributions

LZ and DL conceived of the paper; KQ, XJ and ZL wrote the initial draft of the paper and generated the figures and tables; JZ, PF, YS and NB edited and revised the paper. All authors approved the final paper.

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Correspondence to Dan Liu or Ling-Qiang Zhu.

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Qian, K., Jiang, X., Liu, ZQ. et al. Revisiting the critical roles of reactive astrocytes in neurodegeneration. Mol Psychiatry 28, 2697–2706 (2023). https://doi.org/10.1038/s41380-023-02061-8

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