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Updated: May 27, 2025
09:33
Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
Published on: May 12, 2017
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Aβ42 induces stress granule formation via PACT/PKR pathway
Vijay Sankar Ramasamy1, Alan Benhur Pravin Nathan2, Moon-Chang Choi3
1Department of Cellular and Molecular Medicine, College of Medicine, Chosun University, Gwangju, 61452, Republic of Korea. vijaysankarr@gmail.com.
Scientific Reports
|February 18, 2025
Summary
Alzheimer's disease (AD) protein Amyloid-β42 (Aβ42) triggers stress granule formation via Protein Kinase R (PKR) activation. This process involves PACT and is linked to neurodegeneration, offering new therapeutic targets.
Area of Science:
- Neurobiology
- Molecular Biology
- Cell Biology
Background:
- Stress granule (SG) formation is implicated in neurodegenerative diseases like Alzheimer's disease (AD).
- Amyloid-β42 (Aβ42) is a central factor in AD pathogenesis, known to activate stress pathways.
- The precise role of Aβ42 in SG formation and its underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the SG-inducing properties of Aβ42.
- To elucidate the molecular mechanisms by which Aβ42 triggers SG formation.
- To identify key proteins involved in Aβ42-mediated SG induction.
Main Methods:
- Utilized neuroblastoma (SH-SY5Y) and glioma (U87) cell lines exposed to Aβ42.
- Analyzed phosphorylated eIF2α (p-eIF2α) levels and overall protein translation.
- Employed knockout (KO) cell lines for eIF2α kinases and proximity ligation assay (PLA).
Main Results:
- Aβ42 significantly induced SG formation in both cell lines.
- Elevated p-eIF2α levels were observed, while global protein translation remained constant.
- Monomeric and oligomeric Aβ42 were more potent SG inducers than fibrillar forms.
- Aβ-induced SG formation was dependent on Protein Kinase R (PKR) and involved PACT.
- PACT and PKR showed close proximity in Aβ-treated cells and AD mouse hippocampus.
Conclusions:
- Aβ42 promotes SG formation through the activation of PKR kinase.
- PACT is essential for Aβ42-induced SG formation, highlighting a novel molecular pathway.
- These findings provide insights into AD pathogenesis and potential therapeutic strategies targeting SGs.
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