Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss
Patients with Alzheimer’s disease suffer from a decrease in brain mass and a prevalence of amyloid-β plaques. These plaques are thought to play a role in disease progression, but their exact role is not entirely established. We developed an optogenetic model to induce amyloid-β intracellular oligome...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/2/281 |
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| author | Prameet Kaur Ellora Hui Zhen Chua Wen Kin Lim Jiarui Liu Nathan Harmston Nicholas S. Tolwinski |
| author_facet | Prameet Kaur Ellora Hui Zhen Chua Wen Kin Lim Jiarui Liu Nathan Harmston Nicholas S. Tolwinski |
| author_sort | Prameet Kaur |
| collection | DOAJ |
| description | Patients with Alzheimer’s disease suffer from a decrease in brain mass and a prevalence of amyloid-β plaques. These plaques are thought to play a role in disease progression, but their exact role is not entirely established. We developed an optogenetic model to induce amyloid-β intracellular oligomerization to model distinct disease etiologies. Here, we examine the effect of Wnt signaling on amyloid in an optogenetic, <i>Drosophila</i> gut stem cell model. We observe that Wnt activation rescues the detrimental effects of amyloid expression and oligomerization. We analyze the gene expression changes downstream of Wnt that contribute to this rescue and find changes in aging related genes, protein misfolding, metabolism, and inflammation. We propose that Wnt expression reduces inflammation through repression of Toll activating factors. We confirm that chronic Toll activation reduces lifespan, but a decrease in the upstream activator Persephone extends it. We propose that the protective effect observed for lithium treatment functions, at least in part, through Wnt activation and the inhibition of inflammation. |
| first_indexed | 2024-03-10T01:44:20Z |
| format | Article |
| id | doaj.art-8b64a16f5e3e4962a0df8a123b0e5647 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:44:20Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8b64a16f5e3e4962a0df8a123b0e56472023-11-23T13:18:59ZengMDPI AGCells2073-44092022-01-0111228110.3390/cells11020281Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell LossPrameet Kaur0Ellora Hui Zhen Chua1Wen Kin Lim2Jiarui Liu3Nathan Harmston4Nicholas S. Tolwinski5Division of Science, Yale-NUS College, Singapore 138527, SingaporeDivision of Science, Yale-NUS College, Singapore 138527, SingaporeDivision of Science, Yale-NUS College, Singapore 138527, SingaporeDivision of Science, Yale-NUS College, Singapore 138527, SingaporeDivision of Science, Yale-NUS College, Singapore 138527, SingaporeDivision of Science, Yale-NUS College, Singapore 138527, SingaporePatients with Alzheimer’s disease suffer from a decrease in brain mass and a prevalence of amyloid-β plaques. These plaques are thought to play a role in disease progression, but their exact role is not entirely established. We developed an optogenetic model to induce amyloid-β intracellular oligomerization to model distinct disease etiologies. Here, we examine the effect of Wnt signaling on amyloid in an optogenetic, <i>Drosophila</i> gut stem cell model. We observe that Wnt activation rescues the detrimental effects of amyloid expression and oligomerization. We analyze the gene expression changes downstream of Wnt that contribute to this rescue and find changes in aging related genes, protein misfolding, metabolism, and inflammation. We propose that Wnt expression reduces inflammation through repression of Toll activating factors. We confirm that chronic Toll activation reduces lifespan, but a decrease in the upstream activator Persephone extends it. We propose that the protective effect observed for lithium treatment functions, at least in part, through Wnt activation and the inhibition of inflammation.https://www.mdpi.com/2073-4409/11/2/281Alzheimer’s diseaseamyloid-βWnt<i>Drosophila</i> |
| spellingShingle | Prameet Kaur Ellora Hui Zhen Chua Wen Kin Lim Jiarui Liu Nathan Harmston Nicholas S. Tolwinski Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss Cells Alzheimer’s disease amyloid-β Wnt <i>Drosophila</i> |
| title | Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss |
| title_full | Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss |
| title_fullStr | Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss |
| title_full_unstemmed | Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss |
| title_short | Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss |
| title_sort | wnt signaling rescues amyloid beta induced gut stem cell loss |
| topic | Alzheimer’s disease amyloid-β Wnt <i>Drosophila</i> |
| url | https://www.mdpi.com/2073-4409/11/2/281 |
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