ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Allele-specific RNAi mitigates phenotypic progression in a transgenic model of Alzheimer's disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges.Frontiers in aging neuroscience · 2026Review
- Functional verification and allele-specific silencing of a novel AKT3 variant that causes megalencephaly, polymicrogyria and intractable epilepsy.Journal of human genetics · 2025Article
- TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.Genome biology · 2024Article
- Allele-specific silencing as therapy for familial amyotrophic lateral sclerosis caused by the p.G376DBrain communications · 2022Article
- Inflammation and Alzheimer's Disease: Mechanisms and Therapeutic Implications by Natural Products.Mediators of inflammation · 2021Review
- Allele-specific silencing therapy for Dynamin 2-related dominant centronuclear myopathy.EMBO molecular medicine · 2018Article
- Interaction of the polyglutamine protein ataxin-3 with Rad23 regulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3.Human molecular genetics · 2017Article
- Generation of a new transgenic mouse model for assessment of tau gene silencing therapies.Alzheimer's research & therapy · 2016Article
- A novel measurement of allele discrimination for assessment of allele-specific silencing by RNA interference.Molecular biology reports · 2014Article
- Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23.Nature communications · 2014Article
- Aberrant RNA homeostasis in amyotrophic lateral sclerosis: potential for new therapeutic targets?Neurodegenerative disease management · 2014Article
- Allele-specific knockdown of ALS-associated mutant TDP-43 in neural stem cells derived from induced pluripotent stem cells.PloS one · 2014Article
- RNA interference mitigates motor and neuropathological deficits in a cerebellar mouse model of Machado-Joseph disease.PloS one · 2014Article
- RNA silencing of genes involved in Alzheimer's disease enhances mitochondrial function and synaptic activity.Biochimica et biophysica acta · 2013Article
- Synthetic nucleic acids delivered by exosomes: a potential therapeutic for generelated metabolic brain diseases.Metabolic brain disease · 2013Review
- Silencing mutant ATXN3 expression resolves molecular phenotypes in SCA3 transgenic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Acat1 knockdown gene therapy decreases amyloid-β in a mouse model of Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Recent advances in RNA interference therapeutics for CNS diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2013Review
- Disease-causing allele-specific silencing by RNA interference.Pharmaceuticals (Basel, Switzerland) · 2013Article
- What's hAPPening at synapses? The role of amyloid β-protein precursor and β-amyloid in neurological disorders.Molecular psychiatry · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Despite recent advances suggesting new therapeutic targets, Alzheimer's disease (AD) remains incurable. Aberrant production and accumulation of the Abeta peptide resulting from altered processing of the amyloid precursor protein (APP) is central to the pathogenesis of disease, particularly in dominantly inherited forms of AD. Thus, modulating the production of APP is a potential route to effective AD therapy. Here, we describe the successful use of an allele-specific RNA interference (RNAi) approach targeting the Swedish variant of APP (APPsw) in a transgenic mouse model of AD. Using recombinant adeno-associated virus (rAAV), we delivered an anti-APPsw short-hairpin RNA (shRNA) to the hippocampus of AD transgenic mice (APP/PS1). In short- and long-term transduction experiments, reduced levels of APPsw transprotein were observed throughout targeted regions of the hippocampus while levels of wild-type murine APP remained unaltered. Moreover, intracellular production of transfer RNA (tRNA)-valine promoter-driven shRNAs did not lead to detectable neuronal toxicity. Finally, long-term bilateral hippocampal expression of anti-APPsw shRNA mitigated abnormal behaviors in this mouse model of AD. The difference in phenotype progression was associated with reduced levels of soluble Abeta but not with a reduced number of amyloid plaques. Our results support the development of allele-specific RNAi strategies to treat familial AD and other dominantly inherited neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.