ArticleProceedings of the National Academy of Sciences of the United States of America2023
ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain.Cell reports. Medicine · 2026Article
- Pharmacologic inhibition of PCBP2 biomolecular condensates relieves Alzheimer's disease.Nature communications · 2025Article
- The Role of Gene Expression Dysregulation in the Pathogenesis of Mucopolysaccharidosis: A Comparative Analysis of Shared and Specific Molecular Markers in Neuronopathic and Non-Neuronopathic Types of the Disease.International journal of molecular sciences · 2024Article
- Genome-based discovery of pachysiphine synthases in Tabernaemontana elegans.The Plant journal : for cell and molecular biology · 2024Article
- SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Therapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease.Pharmaceutics · 2023Review
- Quantification of AMPA receptor subunits and RNA editing-related proteins in the J20 mouse model of Alzheimer's disease by capillary western blotting.Frontiers in molecular neuroscience · 2023Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5'UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5'UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5'UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5'UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.
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