ArticleBrain research2011
An α-synuclein AAV gene silencing vector ameliorates a behavioral deficit in a rat model of Parkinson's disease, but displays toxicity in dopamine neurons.
Article in Brain research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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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.
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Who cites it
71 citing papers in PubMed, 112 citations in OpenAlex.
- Oligodendroglial somatic SNCA copy number gains are associated with inclusions and disease onset in multiple system atrophy.Acta neuropathologica · 2026Article
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- α-Synuclein expression is required for somatodendritic dopamine release and immediate early gene induction.Science advances · 2026Article
- Targeted α-Synuclein mRNA Degradation by PMO-Based RNA-Degrading Chimeras.bioRxiv : the preprint server for biology · 2025Article
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- Nose-to-brain siRNA delivery by PEI/PPI-based nanoparticles reduces α-synuclein expression in a Parkinson's disease mouse model.Molecular therapy. Nucleic acids · 2025Article
- Nose-to-brain drug delivery: from bench to bedside.Translational neurodegeneration · 2025Review
- Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.Cellular and molecular neurobiology · 2025Review
- Recent developments in gene therapy for Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Toxic interactions between dopamine, α-synuclein, monoamine oxidase, and genes in mitochondria of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Neuronal-type-specific epigenome editing to decreaseMolecular therapy. Nucleic acids · 2024Article
- Recalibrating the Why and Whom of Animal Models in Parkinson Disease: A Clinician's Perspective.Brain sciences · 2024Review
- Epigenetic editing for autosomal dominant neurological disorders.Frontiers in genome editing · 2024Review
- α-Synuclein in synaptic function and dysfunction.Trends in neurosciences · 2023Review
- Intronic enhancers of the humanScience advances · 2022Article
- Therapeutics in the Pipeline TargetingPharmacological reviews · 2022Review
- Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies.Frontiers in neurology · 2022Review
- The AKT modulator A-443654 reduces α-synuclein expression and normalizes ER stress and autophagy.The Journal of biological chemistry · 2021Article
- Nanotechnology-Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID-19 Vaccines.Small methods · 2021Review
- Understanding the Potential of Genome Editing in Parkinson's Disease.International journal of molecular sciences · 2021Review
11 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Effects of silencing ectopically expressed hSNCA in rat substantia nigra (SN) were examined as a novel therapeutic approach to Parkinson's disease (PD). AAV-hSNCA with or without an AAV harboring a short-hairpin (sh)RNA targeting hSNCA or luciferase was injected into one SN. At 9weeks, hSNCA-expressing rats had reduced SN dopamine (DA) neurons and exhibited a forelimb deficit. AAV-shRNA-SNCA silenced hSNCA and protected against the forelimb deficit. However, AAV-shRNA-SNCA also led to DA neuron loss suggesting undesirable effects of chronic shRNA expression. Effects on nigrostriatal-projecting neurons were examined using a retrograde tract tracer. Loss of striatal-projecting DA neurons was evident in the vector injection site, whereas DA neurons outside this site were lost in hSNCA-expressing rats, but not in hSNCA-silenced rats. These observations suggest that high levels of shRNA-SNCA were toxic to DA neurons, while neighboring neurons exposed to lower levels were protected by hSNCA gene silencing. Also, data collected on DA levels suggest that neurons other than or in addition to nigrostriatal DA neurons contributed to protection of forelimb use. Our observations suggest that while hSNCA gene silencing in DA neurons holds promise as a novel PD therapy, further development of silencing technology is required.
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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.