Academic Journal
Aβ42 induces stress granule formation via PACT/PKR pathway
| Title: | Aβ42 induces stress granule formation via PACT/PKR pathway |
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| Authors: | Vijay Sankar Ramasamy, Alan Benhur Pravin Nathan, Moon-Chang Choi, Sung-Hak Kim, Takbum Ohn |
| Source: | Scientific Reports, Vol 15, Iss 1, Pp 1-12 (2025) |
| Publisher Information: | Nature Portfolio, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Aβ42, Amyloid-β, Stress granule, PKR kinase, Alzheimer’s, Stress signaling, Medicine, Science |
| More Details: | Abstract Stress granule (SG) formation has been linked to several neurodegenerative disorders, such as Alzheimer’s disease (AD). Amyloid-β42 (Aβ42) is a key player in the pathogenesis of AD and is known to trigger various stress-related signaling pathways. However, the impact of Aβ on SG formation has not been fully understood. The primary aim of this study is to analyze the SG-inducing properties of Aβ42 and to uncover the molecular mechanisms underlying this process. Our results revealed that exposure to 20 μM Aβ42 led to a significant SG formation in neuroblastoma-derived (SH-SY5Y) and glioma-derived (U87) cell lines. Interestingly, we observed elevated levels of p-eIF2α, while overall protein translation levels remained unchanged. Monomeric and oligomeric forms of Aβ42 exhibited a 4–5 times stronger ability to induce SG formation compared to fibrillar forms. Additionally, treatment with familial mutants of Aβ42 (Dutch and Flemish) showed distinct effects on SG induction. Moreover, our findings using eIF2α kinases knockout (KO) cell lines demonstrated that Aβ-induced SG formation is primarily dependent on Protein Kinase R (PKR). Subsequent proximity ligation assay (PLA) analysis revealed a close proximity of PACT and PKR in Aβ-treated cells and in AD mouse hippocampus. Taken together, our study suggests that Aβ42 promotes SG formation through PKR kinase activation, which in turn requires PACT involvement. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-025-88380-y |
| Access URL: | https://doaj.org/article/50d67262b68b48149f4c7c579757f88e |
| Accession Number: | edsdoj.50d67262b68b48149f4c7c579757f88e |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-025-88380-y |
| Published in: | Scientific Reports |
| Language: | English |