RNA-binding activity of PHGDH drives amyloid-beta production in a human brain organoid model of sporadic Alzheimer's disease - PubMed
5 days ago
- #Alzheimer's disease
- #RNA-binding
- #Amyloid-beta
- PHGDH's RNA-binding activity drives amyloid-beta (Aβ) production in sporadic Alzheimer's disease (sAD).
- PHGDH binds the 3'UTR of EIF2AK1 mRNA, facilitating EIF2AK1-EIF2α interaction and phosphorylation.
- This process selectively promotes BACE1 translation, the key enzyme for Aβ generation.
- PHGDH overexpression increases BACE1 and Aβ in neurons and astrocytes across models, independent of its enzymatic role.
- The PHGDH-EIF2AK1-EIF2α-BACE1 axis is identified as a key driver of early amyloid pathology in sAD.