ArticleMovement disorders : official journal of the Movement Disorder Society2014
Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice.
Article in Movement disorders : official journal of the Movement Disorder Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 282 papers.
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282 citing papers in PubMed, 496 citations in OpenAlex.
- Brain region-resolved pharmacodynamics of an antisense oligonucleotide targeting human SNCA 3'UTR in BAC-hSNCA rats.Translational neurodegeneration · 2026Article
- Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Exosome-Mediated Delivery of PROTACs for Targeted Protein Degradation in Cancer, Neurodegenerative, Infectious, and Inflammatory Diseases.Journal of cellular and molecular medicine · 2026Review
- Engineering Biomimetic 3D Microenvironments for Extracellular Vesicle Programming Toward Clinical Translation.International journal of molecular sciences · 2026Review
- Dynamic integration of skeletal muscle signals via extracellular vesicles in motor neuron diseases.Acta neuropathologica communications · 2026Review
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
- A Comparative Analysis of iPSC, MSC, and 293T-Derived Exosomes for Parkinson's Disease Therapy.International journal of molecular sciences · 2026Article
- Ion channel and biophysical properties of extracellular vesicles.The Journal of biological chemistry · 2026Review
- Peripheral immunochemical considerations in Parkinson disease: sources, targets and crosstalk mechanisms.Journal of translational medicine · 2026Review
- Loading of therapeutic cell penetrating peptides into extracellular vesicles for pulmonary fibrosis.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Mitochondrial Dynamics-Related Gene Regulation by Epigenetic Suppression of GCN5 Exerts Neuroprotective Effects in Rotenone-Induced Parkinson's Disease Model.Molecular neurobiology · 2026Article
- The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Bioinspired and Biomimetic Nanocarriers: Advances in Exosomes and Cell-Membrane-Coated Systems for Therapeutic Applications.International journal of nanomedicine · 2026Review
- Mesenchymal stem cell-derived exosomes in myocardial infarction repair: therapeutic potential and scaffold-based delivery strategies.Frontiers in pharmacology · 2026Review
- Extracellular vesicles as prognostic biomarkers: results of a neoadjuvant chemoimmunotherapy clinical trial in stage IIIA (N2) non-small-cell lung cancer (SAKK 16/14).Frontiers in immunology · 2026Article
- Mesenchymal stromal cells and paracrine modulation of neuroplasticity in the central nervous system.EXCLI journal · 2026Review
- Microneedle-Enabled Exosome Therapy: From Tumor Targeting to Precision Treatment of Complex Diseases.International journal of nanomedicine · 2026Review
- The role of exosomes as oligonucleotide delivery system for managing α-synuclein in Parkinson's disease: A systematic review ofMolecular therapy. Nucleic acids · 2025Article
- Novel Translational Concept: Axon-to-Muscle Exosomal Signaling as an Emerging Therapeutic Target in Spinal Muscular Atrophy.Biomedicines · 2025Review
- Insights into the Versatile Role of Extracellular Vesicles in the Treatment of CNS Disorders.Molecular neurobiology · 2025Review
222 more citing papers are in PubMed but not listed here.
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10 authors at 4 institutions in 3 countries.
Funding
Abstract
Alpha-synuclein (α-Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that α-Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing α-Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used α-Syn small interfering RNA (siRNA) to reduce total and aggregated α-Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease α-Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation-mimic S129D α-Syn, which exhibits aggregation. In normal mice we detected significantly reduced α-Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG-exosomes loaded with siRNA to α-Syn. In S129D α-Syn transgenic mice we found a decreased α-Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG-exosome delivery of siRNA to delay and reverse brain α-Syn pathological conditions.
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