1. Academic Validation
  2. Mouse serum albumin induces neuronal apoptosis and tauopathies

Mouse serum albumin induces neuronal apoptosis and tauopathies

  • Acta Neuropathol Commun. 2024 Apr 23;12(1):66. doi: 10.1186/s40478-024-01771-6.
Sheng-Jie Hou # 1 2 Ya-Ru Huang # 1 Jie Zhu 1 2 Ying-Bo Jia 1 Xiao-Yun Niu 3 Jin-Ju Yang 1 Xiao-Lin Yu 1 Xiao-Yu Du 1 2 Shi-Yu Liang 1 2 Fang Cui 1 2 Ling-Jie Li 1 2 Chen Tian 1 2 Rui-Tian Liu 4
Affiliations

Affiliations

  • 1 National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, 100190, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Ningxia University, Yinchuan, 750021, Ningxia, China.
  • 4 National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, 100190, China. rtliu@ipe.ac.cn.
  • # Contributed equally.
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.

Keywords

Apoptosis; Mouse serum albumin; Neuroinflammation; Tau phosphorylation.

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