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Open Access 01-12-2024 | Research

Mouse serum albumin induces neuronal apoptosis and tauopathies

Authors: Sheng-jie Hou, Ya-ru Huang, Jie Zhu, Ying-bo Jia, Xiao-yun Niu, Jin-ju Yang, Xiao-lin Yu, Xiao-yu Du, Shi-yu Liang, Fang Cui, Ling-jie Li, Chen Tian, Rui-tian Liu

Published in: Acta Neuropathologica Communications | Issue 1/2024

Abstract

The elderly frequently present impaired blood–brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

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Title: Mouse serum albumin induces neuronal apoptosis and tauopathies
Authors: Sheng-jie Hou
Ya-ru Huang
Jie Zhu
Ying-bo Jia
Xiao-yun Niu
Jin-ju Yang
Xiao-lin Yu
Xiao-yu Du
Shi-yu Liang
Fang Cui
Ling-jie Li
Chen Tian
Rui-tian Liu
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-024-01771-6

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Mouse serum albumin induces neuronal apoptosis and tauopathies

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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