Protein argonaute-1

Protein argonaute-1 (AGO1) is an RNA-binding protein essential for RNA-mediated gene silencing, including microRNA (miRNA) and short interfering RNA (siRNA) pathways. It binds short regulatory RNAs and represses translation of complementary mRNAs, while also participating in transcriptional gene silencing of promoter regions (UniProt: Q9UL18). AGO1 functions broadly in post-transcriptional gene regulation across tissues and is linked to neurodevelopmental processes.

AGO1 is associated with neurodevelopmental disorder with language delay and behavioral abnormalities (NEDLBAS), an autosomal dominant condition characterized by developmental delay, intellectual disability, speech and motor delay, and autistic features, with seizures in approximately half of cases (UniProt: Q9UL18, MIM 620292).

In Alzheimer's disease, AGO1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change +0.33), based on quantitative proteomics of four subcellular fractions (Chaparral AD proteomics). This elevation suggests altered miRNA-mediated gene silencing activity may contribute to AD pathology.