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Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

FOXO4-DRI Key Research Facts Full name: FOXO4 D-Retro-Inverso peptide (FOXO4-DRI) Classification: Cell-penetrating senolytic peptide FOXO4/p53 protein-protein interaction inhibitor Design: D-retro-inverso isoform of FOXO4s p53-binding domain reversed sequence with all D-amino acids Binding target: p53 transactivation domain 2 (TAD2) displaces FOXO4 from the FOXO4-p53 complex Mechanism: FOXO4-DRI binds p53 TAD2 p53 nuclear exclusion p53 mitochondrial translocation BAX activation caspase-3 cleavage senescent cell-selective apoptosis Selectivity basis: FOXO4 is upregulated in senescent cells but expressed at low levels in most non-senescent adult cells selectivity is mechanistically conferred D-amino acid advantage: Proteolytic stability resistant to intracellular peptidases that would rapidly degrade equivalent L-amino acid sequences Structural characterisation: NMR structural models of FOXO4-DRI/p53TAD2 complex resolved (Nature Communications, 2025) confirms disordered-to-ordered transition upon binding Research cell types studied: IMR90 fibroblasts, TM3 Leydig cells, endothelial cells, chondrocytes, keloid fibroblasts, HCT116 cancer cells In vitro working concentration: 25 M used in multiple published studies for senescent cell apoptosis induction What Does FOXO4-DRI Do in Research

In an email, Jong-Hwei Su Pang, a professor at Chang Gung Universitys Graduate Institute of Clinical Medical Sciences, wrote that the peptide might be produced by stomach microbes, as its amino acid sequence doesnt appear in the human genome

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A positive control analysis was conducted to validate the genetic instruments for GLP-1R by verifying the association of genetic instruments from eQTLs with type 2 diabetes, given that GLP-1R agonists are FDA-approved for blood glucose and weight control