TREM2‐dependent microglial function is essential for remyelination and subsequent neuroprotection
Name
Glia - 2023 - Wang - TREM2‐dependent microglial function is essential for remyelination and subsequent neuroprotection.pdf
Description
Published version
Size
3.78 MB
Format
Adobe PDF
Checksum (MD5)
04faafa6be803964293c00d31a5b9222
Author(s)
Wang, Yuanyuan
Kyauk, Roxanne V
Shen, Yun‐An A
Xie, Luke
Reichelt, Mike
Lin, Han
Jiang, Zhiyu
Ngu, Hai
Shen, Kimberle
Greene, Jacob J
Date Issued
May 2023
Journal
Glia
Publisher
Wiley
Citation
Wang, Yuanyuan, Kyauk, Roxanne V, Shen, Yun‐An A, Xie, Luke, Reichelt, Mike et al. 2023. "TREM2‐dependent microglial function is essential for remyelination and subsequent neuroprotection." Glia, 71 (5).
Version
Final published version
Abstract
Disability in multiple sclerosis (MS) is driven in part by the failure of remyelination and progressive neurodegeneration. Microglia, and specifically triggering receptor expressed on myeloid cells 2 (TREM2), a factor highly expressed in microglia, have been shown to play an important role in remyelination. Here, using a focal demyelination model in the brain, we demonstrate that demyelination is persistent in TREM2 knockout mice, lasting more than 6 weeks after lysolecithin injection and resulting in substantial neurodegeneration. We also find that TREM2 knockout mice exhibit an altered glial response following demyelination. TREM2 knockout microglia demonstrate defects in migration and phagocytosis of myelin debris. In addition, human monocyte-derived macrophages from subjects with a TREM2 mutation prevalent in human disease also show a defect in myelin debris phagocytosis. Together, we highlight the central role of TREM2 signaling in remyelination and neuroprotection. These findings provide insights into how chronic demyelination might lead to axonal damage and could help identify novel neuroprotective therapeutic targets for MS.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1002/glia.24335
