Wnt signaling rescues amyloid beta-induced gut stem cell loss

Kaur, Prameet, Chua, Ellora Hui Zhen, Lim, Wen Kin, Liu, Jiarui, Harmston, Nathan and Tolwinski, Nicholas 2022. Wnt signaling rescues amyloid beta-induced gut stem cell loss. Cells 11 (2) , 281. 10.3390/cells11020281

PDF - Published Version Available under License Creative Commons Attribution. Download (37MB)

Abstract

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, Drosophila 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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Publisher:	MDPI
ISSN:	2073-4409
Date of First Compliant Deposit:	30 August 2023
Date of Acceptance:	13 January 2022
Last Modified:	01 Sep 2023 01:41
URI:	https://orca.cardiff.ac.uk/id/eprint/161876

Actions (repository staff only)

Edit Item