ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Acat1 knockdown gene therapy decreases amyloid-β in a mouse model of Alzheimer's disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 101 citations in OpenAlex.
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Advancements in Gene Delivery using Nucleic Acid Loaded Nanoparticles for Region Specific Delivery in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer's Pathogenesis.Molecular neurobiology · 2026Review
- Alzheimer's disease pathogenesis: standing at the crossroad of lipid metabolism and immune response.Molecular neurodegeneration · 2025Review
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Aging Apolipoprotein E4 Mice Alters Their Brains' Inflammatory Profiles.International journal of molecular sciences · 2024Article
- The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4.bioRxiv : the preprint server for biology · 2024Article
- Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer's disease.Frontiers in pharmacology · 2024Review
- Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity.Molecular neurodegeneration · 2023Article
- Mitochondrial heterogeneity in diseases.Signal transduction and targeted therapy · 2023Review
- siRNA drug delivery across the blood-brain barrier in Alzheimer's disease.Advanced drug delivery reviews · 2023Review
- Stealth Liposomes Encapsulating a Potent ACAT1/SOAT1 Inhibitor F12511: Pharmacokinetic, Biodistribution, and Toxicity Studies in Wild-Type Mice and Efficacy Studies in Triple Transgenic Alzheimer's Disease Mice.International journal of molecular sciences · 2023Article
- Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- ACAT1/SOAT1 Blockade Suppresses LPS-Mediated Neuroinflammation by Modulating the Fate of Toll-like Receptor 4 in Microglia.International journal of molecular sciences · 2023Article
- Acute ACAT1/SOAT1 Blockade Increases MAM Cholesterol and Strengthens ER-Mitochondria Connectivity.International journal of molecular sciences · 2023Article
- Review
- Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise.The FEBS journal · 2023Review
- Advances toward precision therapeutics for developmental and epileptic encephalopathies.Frontiers in neuroscience · 2023Review
- Facile method to incorporate high-affinity ACAT/SOAT1 inhibitor F12511 into stealth liposome-based nanoparticle and demonstration of its efficacy in blocking cholesteryl ester biosynthesis without overt toxicity in neuronal cell culture.Journal of neuroscience methods · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Both genetic inactivation and pharmacological inhibition of the cholesteryl ester synthetic enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1) have shown benefit in mouse models of Alzheimer's disease (AD). In this study, we aimed to test the potential therapeutic applications of adeno-associated virus (AAV)-mediated Acat1 gene knockdown in AD mice. We constructed recombinant AAVs expressing artificial microRNA (miRNA) sequences, which targeted Acat1 for knockdown. We demonstrated that our AAVs could infect cultured mouse neurons and glia and effectively knockdown ACAT activity in vitro. We next delivered the AAVs to mouse brains neurosurgically, and demonstrated that Acat1-targeting AAVs could express viral proteins and effectively diminish ACAT activity in vivo, without inducing appreciable inflammation. We delivered the AAVs to the brains of 10-month-old AD mice and analyzed the effects on the AD phenotype at 12 months of age. Acat1-targeting AAV delivered to the brains of AD mice decreased the levels of brain amyloid-β and full-length human amyloid precursor protein (hAPP), to levels similar to complete genetic ablation of Acat1. This study provides support for the potential therapeutic use of Acat1 knockdown gene therapy in AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.