Presenilin mutations disrupt iron homeostasis to promote ferroptosis mediated neurodegeneration in Caenorhabditis elegans.

ABSTRACT: Iron is a vital trace element involved in numerous physiological processes, but it becomes toxic when present in excess. Disruption of iron balance in the brain has been linked to the development of neurodegenerative diseases such as Alzheimer's disease (AD), though the underlying mechanisms remain poorly understood. Familial forms of AD are primarily caused by mutations in presenilin, which are known to disturb cellular calcium homeostasis. However, the role of iron in presenilin-related neurodegeneration has not been fully explored. Using C. elegans as a model organism, we investigated the function of SEL-12, the worm ortholog of presenilin, and found that loss of SEL-12 leads to elevated iron levels and increased expression of FTN-2/ferritin, an iron-sequestering protein. Notably, reduc

SUBMITTER: Ryan KC 

PROVIDER: S-EPMC12639444 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature