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

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

Abstract 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-permeab...

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Main Authors: Jesus Campagna, Sujyoti Chandra, Bruce Teter, Whitaker Cohn, Johnny Pham, Young-Sug Kim, Barbara Jagodzinska, Kanagasabai Vadivel, Parvez Alam, Tina Bilousova, Malaney Young, Chris Elias, Juan Marcucci, Ilinca Flacau, Ainsley Jackman, Samar Padder, Dongwook Wi, Chunni Zhu, Patricia Spilman, Michael E Jung, Dale E Bredesen, Varghese John
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
Apolipoprotein E4
Sirtuin 1
SirT1
PRMT5
NFYb
SirT1 enhancer
Online Access:https://doi.org/10.1038/s41598-025-96131-2
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