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Peer-reviewedCC BY 4.0Translational Neurodegeneration

Brain clearance of protein aggregates in degenerative diseases: the role of microglia and astrocytes

  • Min Xiong1
  • Yeyu Huang1
  • Haiqiang Jiang2
  • Zhentao Zhang1,3,4,5
5 affiliations
  1. 1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060 China
  2. 2Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355 China
  3. 3State Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Life Sciences, Wuhan University, Wuhan, 430000 China
  4. 4TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430000 China
  5. 5Hubei Provincial Clinical Medical Research Center for Neurodegenerative Diseases, Wuhan, 430060 China
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Abstract

Protein aggregation and impaired clearance constitute central pathological hallmarks of numerous neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Misfolded proteins, both extracellular and intracellular, disrupt proteostasis and contribute to synaptic dysfunction, neuroinflammation, and neuronal loss. Within the central nervous system, glial cells serve as the primary mediators of pathological protein clearance. Microglia detect, phagocytose, and degrade aggregated proteins. However, under chronic pathological stress, microglial function turns from clearing pathological proteins to paradoxically facilitating their spread. Astrocytes, which provide metabolic and homeostatic support for neurons, also participate in the clearance of aggregates through phagocytosis and glymphatic drainage. Critically, crosstalk between astrocytes and microglia enhances the clearance: microglia can recruit and process aggregates internalized by astrocytes, while astrocyte-derived signals modulate the microglial phagocytic activity. Aging, genetic risk factors, or sustained neuroinflammation may reduce the efficiency of glial removal of aggregates and accelerate disease progression. Understanding the cellular and molecular underpinnings of microglial and astrocytic clearance pathways is essential for developing therapies aimed at restoring proteostasis and mitigating neurodegeneration.

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Cite

BibTeXRIS
BibTeX
@article{xiong2026brain,
  title = {{Brain clearance of protein aggregates in degenerative diseases: the role of microglia and astrocytes}},
  author = {Min Xiong and Yeyu Huang and Haiqiang Jiang and Zhentao Zhang},
  journal = {Translational Neurodegeneration},
  year = {2026},
  month = nov,
  doi = {10.1186/s40035-026-00592-y},
  url = {https://doi.org/10.1186/s40035-026-00592-y},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Brain clearance of protein aggregates in degenerative diseases: the role of microglia and astrocytes
AU  - Min Xiong
AU  - Yeyu Huang
AU  - Haiqiang Jiang
AU  - Zhentao Zhang
PY  - 2026
DA  - 2026/11/04
JO  - Translational Neurodegeneration
DO  - 10.1186/s40035-026-00592-y
UR  - https://doi.org/10.1186/s40035-026-00592-y
AB  - Protein aggregation and impaired clearance constitute central pathological hallmarks of numerous neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Misfolded proteins, both extracellular and intracellular, disrupt proteostasis and contribute to synaptic dysfunction, neuroinflammation, and neuronal loss. Within the central nervous system, glial cells serve as the primary mediators of pathological protein clearance. Microglia detect, phagocytose, and degrade aggregated proteins. However, under chronic pathological stress, microglial function turns from clearing pathological proteins to paradoxically facilitating their spread. Astrocytes, which provide metabolic and homeostatic support for neurons, also participate in the clearance of aggregates through phagocytosis and glymphatic drainage. Critically, crosstalk between astrocytes and microglia enhances the clearance: microglia can recruit and process aggregates internalized by astrocytes, while astrocyte-derived signals modulate the microglial phagocytic activity. Aging, genetic risk factors, or sustained neuroinflammation may reduce the efficiency of glial removal of aggregates and accelerate disease progression. Understanding the cellular and molecular underpinnings of microglial and astrocytic clearance pathways is essential for developing therapies aimed at restoring proteostasis and mitigating neurodegeneration.
SN  - 2047-9158
ER  -