Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model - PubMed
4 hours ago
- #Alzheimer's disease
- #Yip7
- #Aβ42
- Intraneuronal Aβ accumulation is an early pathogenic event in Alzheimer's disease (AD).
- The serine protease Yip7 shows neuroprotective effects in a Drosophila AD model.
- Yip7 overexpression mitigates Aβ42-induced deficits like locomotor decline, proteostasis impairment, and neuronal death.
- Yip7 localizes to endosomal/lysosomal compartments and its neuroprotection depends on subcellular localization, not catalytic activity.
- Yip7 binds intracellular Aβ42, increasing its neuronal retention and reducing toxicity.
- Transcriptomics reveals Yip7 suppresses Aβ-upregulated genes, including ribosomal proteins and molecular chaperones.
- The study suggests intracellular Aβ sequestration as a novel strategy to mitigate neurotoxicity.