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Discovery of an ApoE4-targeted small-molecule SirT1 enhancer for the treatment of Alzheimer’s disease

23 Apr 2025

Abstract excerpt

Decreased expression of sirtuin 1 (SirT1) has been implicated in Alzheimer's disease (AD), and as we previously reported, is related to transcriptional repression by the major risk factor for sporadic AD, apolipoprotein E4 (ApoE4). Herein we describe the discovery of an orally brain-permeable small-molecule, DDL-218, that enhanced SirT1 in ApoE4-expressing neuronal cells and a murine AD model. DDL-218 increased...

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PMID: 40269061
DOI: 10.1038/s41598-025-96131-2

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