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Open Access 16-01-2024 | Neuromyelitis Optica Spectrum Disease | Original Article

Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder

Authors: Man Chen, Yun-Hui Chu, Wen-Xiang Yu, Yun-Fan You, Yue Tang, Xiao-Wei Pang, Hang Zhang, Ke Shang, Gang Deng, Luo-Qi Zhou, Sheng Yang, Wei Wang, Jun Xiao, Dai-Shi Tian, Chuan Qin

Published in: Neuroscience Bulletin

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Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) accompanied by blood-brain barrier (BBB) disruption. Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD. However, there is limited evidence on the functional relevance of circulating lipids in CNS demyelination, cellular metabolism, and microglial function. Here, we found that serum low-density lipoprotein (LDL) was positively correlated with markers of neurological damage in NMOSD patients. In addition, we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB, directly activating microglia. This activation leads to excessive phagocytosis of myelin debris, inhibition of lipid metabolism, and increased glycolysis, ultimately exacerbating myelin damage. We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD. These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage, highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.
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Metadata
Title
Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder
Authors
Man Chen
Yun-Hui Chu
Wen-Xiang Yu
Yun-Fan You
Yue Tang
Xiao-Wei Pang
Hang Zhang
Ke Shang
Gang Deng
Luo-Qi Zhou
Sheng Yang
Wei Wang
Jun Xiao
Dai-Shi Tian
Chuan Qin
Publication date
16-01-2024
Publisher
Springer Nature Singapore
Published in
Neuroscience Bulletin
Print ISSN: 1673-7067
Electronic ISSN: 1995-8218
DOI
https://doi.org/10.1007/s12264-023-01166-y