Inactivation of SIAH-1 E3 ligase attenuates Aβ toxicity by suppressing ubiquitin-dependent DVE-1 degradation in Caenorhabditis elegans models of Alzheimer's disease.

ABSTRACT: The mitochondrial unfolded protein response (UPR^mt), an evolutionarily conserved proteostasis pathway, plays a critical role in the pathogenesis of Alzheimer's disease (AD), characterized by amyloid-β peptide (Aβ) aggregation. Although the transcription factor DVE-1 regulates UPR^mt activation in Caenorhabditis elegans and has been implicated in Aβ pathology, its regulatory mechanisms under AD-like conditions remain unclear. Here, using the classical C. elegans muscle-specific AD model (CL2006 strain), we observed UPR^mt induction in young adults despite paradoxical depletion of DVE-1 protein concurrent with elevated dve-1 transcript levels. Through integrated genetic and biochemical analyses, we identified SIAH-1, a conserved E3 ubiquitin ligase that partner

SUBMITTER: Sun L 

PROVIDER: S-EPMC12179603 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature