Related Experiment Video
Updated: Apr 21, 2026
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
Amyloid-beta-activated human microglial cells through ER-resident proteins
YongCheol Yoo1, Kyunghee Byun, Taewook Kang
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology , 373-1 Guseong-dong, Daejeon 305-701, Republic of Korea.
Abstract:
Microglial activation in the central nervous system is a key event in the neuroinflammation that accompanies neurodegenerative diseases such as Alzheimer's disease (AD). Among cytokines involved in microglial activation, amyloid β (Aβ) peptide is known to be a key molecule in the induction of diverse inflammatory products, which may lead to chronic inflammation in AD. However, proteomic studies of microglia in AD are limited due to lack of proper cell or animal model systems. In this study, we performed a proteomic analysis of Aβ-stimulated human microglial cells using SILAC (stable isotope labeling with amino acids in cell culture) combined with LC-MS/MS. Results showed that 60 proteins increased or decreased their abundance by 1.5 fold or greater. Among these, ER-resident proteins such as SERPINH1, PDIA6, PDIA3, and PPIB were revealed to be key molecular biomarkers of human microglial activation by validation of the proteomic results by immunostaining, PCR, ELISA, and Western blot. Taken together, our data suggest that ER proteins play an essential role in human microglial activation by Aβ and may be important molecular therapeutic targets for treatment of AD.
Insights
Amyloid beta triggers inflammation in Alzheimer's disease (AD) by activating microglia. This study identified endoplasmic reticulum (ER) proteins as key biomarkers for this microglial activation, offering potential therapeutic targets for AD.
Area of Science:
- Neuroscience
- Immunology
- Proteomics
Background:
- Microglial activation is central to neuroinflammation in Alzheimer's disease (AD).
- Amyloid beta (Aβ) peptide drives microglial activation and chronic inflammation in AD.
- Limited proteomic data exists for microglia in AD models.
Purpose of the Study:
- To conduct a proteomic analysis of Aβ-stimulated human microglial cells.
- To identify key molecular biomarkers of microglial activation in response to Aβ.
- To explore potential therapeutic targets for AD based on microglial activation pathways.
Main Methods:
- Utilized stable isotope labeling with amino acids in cell culture (SILAC) for quantitative proteomic analysis.
- Employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) for protein identification and quantification.
- Validated proteomic findings using immunostaining, PCR, ELISA, and Western blot.
Main Results:
- Identified 60 proteins with a ≥1.5 fold change in abundance upon Aβ stimulation.
- Revealed endoplasmic reticulum (ER)-resident proteins (SERPINH1, PDIA6, PDIA3, PPIB) as key biomarkers.
- Confirmed the role of these ER proteins in human microglial activation.
Conclusions:
- ER proteins are essential in Aβ-induced human microglial activation.
- These ER proteins represent potential molecular therapeutic targets for Alzheimer's disease.
- This study provides novel insights into the proteomic landscape of activated microglia in AD.
