ArticleJournal of translational medicine2023
FTO-targeted siRNA delivery by MSC-derived exosomes synergistically alleviates dopaminergic neuronal death in Parkinson's disease via m6A-dependent regulation of ATM mRNA.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 58 citations in OpenAlex.
- Extracellular vesicles for next-gen therapeutics and drug delivery.Molecular biomedicine · 2026Review
- Interaction between N6-methyladenosine (mGenes & diseases · 2026Review
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- Exosome Biology at the Interface of Neurodegeneration and Therapeutic Innovation.Molecular neurobiology · 2026Review
- Extracellular vesicle-mediated bidirectional communication between the brain and peripheral organs in Alzheimer's disease: evidence, mechanisms, and translational perspectives.Journal of nanobiotechnology · 2026Review
- Epigenetic Dysregulation of the Wnt/β-Catenin Pathway via FTO-m6A in the mPFC Contributes to Autism-Like Behaviors.Molecular neurobiology · 2026Article
- Neuromodulatory role and therapeutic potential of N 6 -methyladenosine RNA methylation in neurodegenerative diseases.Neural regeneration research · 2026Article
- The Role of NMedComm · 2026Review
- Engineered Exosomes: Innovative Strategies for Precision Drug Delivery in Parkinson's Disease.Molecular neurobiology · 2026Review
- The epitranscriptomic m6A RNA modification modulates the synapse in ageing and in a mouse model of synucleinopathy.NPJ Parkinson's disease · 2026Article
- Overcoming Oxidative Stress in Parkinson's Disease: NADPH Oxidase 4 (NOX4) as a Potential Therapeutic Target.Antioxidants (Basel, Switzerland) · 2026Review
- Therapeutic Mechanisms of Stem Cell-Derived Exosomes for Neurological Disorders: An Overview.Molecular neurobiology · 2026Review
- Integrating Weighted Gene Co-Expression Network and Differential Expression Analyses to Unveil the Role of RNA m6A Methylation Regulators in Idiopathic Parkinson's Disease in Latin America.Life (Basel, Switzerland) · 2026Article
- Extracellular Vesicles in Tauopathies: Mechanisms and Applications.International journal of molecular sciences · 2026Review
- Review
- The crucial role of N6-methyladenosine modification in acute kidney injury: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Exploring the research landscape of exosomes in Parkinson's disease: a bibliometric analysis.Frontiers in neurology · 2026Article
- A multidimensional landscape of extracellular vesicle-mediated tumor drug resistance: mechanisms, biomarkers, engineered drug delivery, and clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Stem cell extracellular vesicles for neuropsychiatric disorders and translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Colostrum extracellular vesicles are neuroprotective in models of Parkinson's disease.Theranostics · 2026Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundParkinson's disease (PD), characterized by the progressive loss of dopaminergic neurons in the substantia nigra and striatum of brain, seriously threatens human health, and is still lack of effective treatment. Dysregulation of N6-methyladenosine (m6A) modification has been implicated in PD pathogenesis. However, how m6A modification regulates dopaminergic neuronal death in PD remains elusive. Mesenchymal stem cell-derived exosomes (MSC-Exo) have been shown to be effective for treating central nervous disorders. We thus propose that the m6A demethylase FTO-targeted siRNAs (si-FTO) may be encapsulated in MSC-Exo (Exo-siFTO) as a synergistic therapy against dopaminergic neuronal death in PD.
methodsIn this study, the effect of m6A demethylase FTO on dopaminergic neuronal death was evaluated both in vivo and in vitro using a MPTP-treated mice model and a MPP + -induced MN9D cellular model, respectively. The mechanism through which FTO influences dopaminergic neuronal death in PD was investigated with qRT-PCR, western blot, immumohistochemical staining, immunofluorescent staining and flow cytometry. The therapeutic roles of MSC-Exo containing si-FTO were examined in PD models in vivo and in vitro.
resultsThe total m6A level was significantly decreased and FTO expression was increased in PD models in vivo and in vitro. FTO was found to promote the expression of cellular death-related factor ataxia telangiectasia mutated (ATM) via m6A-dependent stabilization of ATM mRNA in dopaminergic neurons. Knockdown of FTO by si-FTO concomitantly suppressed upregulation of α-Synuclein (α-Syn) and downregulation of tyrosine hydroxylase (TH), and alleviated neuronal death in PD models. Moreover, MSC-Exo were utilized to successfully deliver si-FTO to the striatum of animal brain, resulting in the significant suppression of α-Syn expression and dopaminergic neuronal death, and recovery of TH expression in the brain of PD mice.
conclusionsMSC-Exo delivery of si-FTO synergistically alleviates dopaminergic neuronal death in PD via m6A-dependent regulation of ATM mRNA.
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