MicroRNA-124-3p-enriched small extracellular vesicles as a therapeutic approach for Parkinson’s disease

Esteves, Marta; Abreu, Ricardo C. de; Fernandes, Hugo; Serra-Almeida, Catarina; Martins, Patrícia A. T.; Barão, Marta; Cristóvão, Ana Clara; Saraiva, Cláudia; Ferreira, Lino; Bernardino, Liliana

doi:10.1016/j.ymthe.2022.06.003

Cited by 36 publications

(33 citation statements)

References 51 publications

(104 reference statements)

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“…179 Nevertheless, EVs can serve as a model for the identification of targeting moieties directing their tropism to specific brain cells. 180 Labelled with gold NPs to track their biodistribution by computerized tomography, EVs exhibited different biodistributions depending on the brain pathology. 181 High-throughput screening methodologies can therefore be employed for rapid identification of bioactive molecules from EVs.…”

Section: Discussionmentioning

confidence: 99%

Engineering optical tools for remotely controlled brain stimulation and regeneration

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Engineering optical tools for remotely controlled brain stimulation and regeneration

et al. 2023

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“…miRNA mimics and inhibitors have been used to change the endogenous levels of certain miRNAs and regulate cell function [ 63 , 64 ], as in the case of miR-124 [ 65 , 66 ]. The overexpression of miR-124 was shown to act as a neuroprotective factor in Parkinson’s disease [ 67 , 68 ] and in AD [ 62 , 69 ]. In human AD neuronal models with elevated levels of miR-124, we have shown by using an miR-124 mimic and inhibitor that an increase in miR-124 may be associated with mechanisms of defence and adaptation to the pathology [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice

et al. 2022

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with short life expectancy and no effective therapy. We previously identified upregulated miR-124 in NSC-34-motor neurons (MNs) expressing human SOD1-G93A (mSOD1) and established its implication in mSOD1 MN degeneration and glial cell activation. When anti-miR-124-treated mSOD1 MN (preconditioned) secretome was incubated in spinal cord organotypic cultures from symptomatic mSOD1 mice, the dysregulated homeostatic balance was circumvented. To decipher the therapeutic potential of such preconditioned secretome, we intrathecally injected it in mSOD1 mice at the early stage of the disease (12-week-old). Preconditioned secretome prevented motor impairment and was effective in counteracting muscle atrophy, glial reactivity/dysfunction, and the neurodegeneration of the symptomatic mSOD1 mice. Deficits in corticospinal function and gait abnormalities were precluded, and the loss of gastrocnemius muscle fiber area was avoided. At the molecular level, the preconditioned secretome enhanced NeuN mRNA/protein expression levels and the PSD-95/TREM2/IL-10/arginase 1/MBP/PLP genes, thus avoiding the neuronal/glial cell dysregulation that characterizes ALS mice. It also prevented upregulated GFAP/Cx43/S100B/vimentin and inflammatory-associated miRNAs, specifically miR-146a/miR-155/miR-21, which are displayed by symptomatic animals. Collectively, our study highlights the intrathecal administration of the secretome from anti-miR-124-treated mSOD1 MNs as a therapeutic strategy for halting/delaying disease progression in an ALS mouse model.

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“…miR-124-3p has been recognized as a promising therapeutic molecule for PD on account of its neurogenic and neuroprotective effects. The results showed that miR-124-3p-loaded exosomes promoted neuronal differentiation of neural stem cells and the protection of N27 dopaminergic cells against 6-OHDA-induced cytotoxicity [ 171 ].…”

Section: The Application Potential Of Rna-loaded Exosomesmentioning

confidence: 99%

Exosome-Based Carrier for RNA Delivery: Progress and Challenges

Huang

et al. 2023

Pharmaceutics

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In the last few decades, RNA-based drugs have emerged as a promising candidate to specifically target and modulate disease-relevant genes to cure genetic defects. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes have been exploited as a promising vehicle for drug delivery due to their nanoscale size, high stability, high biocompatibility, and low immunogenicity. We reviewed and summarized the progress in the strategy and application of exosome-mediated RNA therapy. The challenges of exosomes as a carrier for RNA drug delivery are also elucidated in this article. RNA molecules can be loaded into exosomes and then delivered to targeted cells or tissues via various biochemical or physical approaches. So far, exosome-mediated RNA therapy has shown potential in the treatment of cancer, central nervous system disorders, COVID-19, and other diseases. To further exploit the potential of exosomes for RNA delivery, more efforts should be made to overcome both technological and logistic problems.

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MicroRNA-124-3p-enriched small extracellular vesicles as a therapeutic approach for Parkinson’s disease

Cited by 36 publications

References 51 publications

Engineering optical tools for remotely controlled brain stimulation and regeneration

Engineering optical tools for remotely controlled brain stimulation and regeneration

Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice

Exosome-Based Carrier for RNA Delivery: Progress and Challenges

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