Extracellular Vesicles as Nanotherapeutics for Parkinson’s Disease
Abstract
:1. Introduction
2. PD Risk Factors are Linked to EV Biology
2.1. Genetic Susceptibility in PD
2.2. Gut Microbiota and PD
2.3. PD Signature Markers in EVs
3. Therapeutic Approaches for the Treatment of PD
Cell Therapies
4. EV-Based Therapeutics for Cell-Free Treatment of PD
4.1. Non-Modified EVs to Arrest the Pathologic Propagation of PD
4.2. EVs and Lipophilic Particles as Drug Delivery System in PD
4.2.1. DA Replacement
4.2.2. Anti-Oxidant Agents
4.2.3. Inhibition of α-Syn Synthesis/Aggregation
4.3. GDNF Therapy
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Donor Cell/Origin | Vesicle Type | In Vitro Model | Outcomes | Route of Administration | In Vivo Model | Outcomes | REF. |
---|---|---|---|---|---|---|---|
MSCs from the dental pulp of human exfoliated deciduous teeth | EVs | ReNCell VM derived DAergic neurons treated with 6-OHDA | Apoptosis suppression | Intranasal injection | 6-OHDA treated rats | Improvements in motor and gait parameters; increase in TH+ neuron density | [234,235] |
None | DA-loaded poly (lactic-coglycolicacid) nanoparticles | None | Systemic injection | 6-OHDA treated rats | Reversion of neurobehavioral and neurochemical impairments; inhibition of ROS production | [236] | |
Serum | DA-loaded EVs | None | Systemic injection | 6-OHDA treated mice | EVs reached the SNpc and the Striatum; increase in DA accumulation and TH+ neuron density; amelioration of behavioral parameters | [237] | |
None | DA-loaded borneol and lactoferrin-modified nanoparticle | None | Intranasal injection | 6-OHDA treated rats | Restoration of striatal DA levels; motor function improvements | [238] | |
Mouse lymphoma EL-4 cell line | Curcumin-loaded EVs | LPS treated RAW 264.7 macrophages | Decrease of IL-6 and TNF-α production | Intraperitoneal injection | LPS treated mice | Reduction of CD11b+ and Gr-1+ cells in lung; lower sera levels of IL-6 and TNF-α | [239] |
Mouse lymphoma EL-4 cell line | Curcumin-loaded EVs | None | Intranasal injection | LPS treated mice | Reduction of microgliosis through apoptosis induction | [240] | |
RAW 264.7 macrophage cell line stably transfected with catalase-carrying plasmid | EVs | None | Systemic injection of cells | 6-OHDA treated mice | Anti-inflammatory and neuroprotective effects; improvements in motor functions | [241] | |
RAW 264.7 macrophage cell line | Catalase-loaded EVs by saponin permeabilization | PC12 neuronal cells treated with 6-OHDA; RAW 264.7 cells treated with LPS and TNF-α | Increase in neuronal viability; decrease in H2O2 levels in macrophage | Intranasal injection | 6-OHDA treated mice | Reduction in microgliosis and astrogliosis; improvement in motor parameters | [242] |
HEK293T cell line engineered to produce more EVs | EVs containing catalase mRNA | CHRNA7-positive Neuro2A cells treated with 6-OHDA; neuronal and microglia co-cultures treated with LPS | Partial recovery of 6-OHDA induced neurotoxicity; rescue of neurotoxicity in LPS treated cells | Intracerebral implantation of EV producing cells | 6-OHDA treated mice | Reduction of ROS-triggered neuroinflammation and rescue of neuronal death within the striatum where 6-OHDA was injected | [243] |
Human astrocytoma 1321N1; primary cortical astrocytes treated with human ApoD | Paraquat treated differentiated SH-SY5Y cells, primary WT or ApoD-KO astrocytes | Increase in neurons and astrocytes viability | None | [244] | |||
Mouse self-dendritic cells transfected with the RVG-Lamp2-flag construct | α-Syn siRNA-loaded EVs | SH-SY5Y expressing human S129D α-Syn-HA | Reduction of α-Syn at protein and mRNA level | Systemic injection | Phosphorylation-mimic S129D α-Syn transgenic mice | Significant short-term decrease in α-Syn mRNA levels in midbrain, striatum, and cortex brain areas | [245] |
Mouse self-dendritic cells | Anti-α-Syn ShRNA-MC-loaded EVs | SH-SY5Y expressing mouse α-Syn-HA | Reduction of S129D α-Syn protein | Systemic injection | Phosphorylation-mimic S129D α-Syn transgenic mice; mice injected of α-Syn pre-formed fibrils | Prolonged down-regulation of S129D α-Syn mRNA lower protein levels; down-regulation of α-Syn expression; neuroprotection | [246] |
None | Ferulic acid diacid: tannic acid anti-oxidant nanoparticles | BV2 microglial cells treated with Ac-α-Syn or A53T α-Syn and/or pro-inflammatory cytokines | Significant decrease of oligomeric aggregated of Ac-α-Syn and A53T α-Syn oligomers; attenuation of microgliosis | None | [247] | ||
Bone marrow stem cell-derived macrophages ex vivo transfected with GDNF-carrying vector | EVs containing GDNF | None | Systemic injection of cells | MTPT and 6-OHDA treated mice | Neuroprotection of DAergic neurons and increased DA production; motor function improvements | [248,249] | |
None | Gelatine-based nanoparticles carrying GDNF-pDNA | None | Intranasal injection | 6-OHDA treated rats | Transfection of resident brain cells with GDNF increase; protection of DAergic neurons and dendritic fibers in SN; motor function improvements | [250] |
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Leggio, L.; Paternò, G.; Vivarelli, S.; L’Episcopo, F.; Tirolo, C.; Raciti, G.; Pappalardo, F.; Giachino, C.; Caniglia, S.; Serapide, M.F.; et al. Extracellular Vesicles as Nanotherapeutics for Parkinson’s Disease. Biomolecules 2020, 10, 1327. https://doi.org/10.3390/biom10091327
Leggio L, Paternò G, Vivarelli S, L’Episcopo F, Tirolo C, Raciti G, Pappalardo F, Giachino C, Caniglia S, Serapide MF, et al. Extracellular Vesicles as Nanotherapeutics for Parkinson’s Disease. Biomolecules. 2020; 10(9):1327. https://doi.org/10.3390/biom10091327
Chicago/Turabian StyleLeggio, Loredana, Greta Paternò, Silvia Vivarelli, Francesca L’Episcopo, Cataldo Tirolo, Gabriele Raciti, Fabrizio Pappalardo, Carmela Giachino, Salvatore Caniglia, Maria Francesca Serapide, and et al. 2020. "Extracellular Vesicles as Nanotherapeutics for Parkinson’s Disease" Biomolecules 10, no. 9: 1327. https://doi.org/10.3390/biom10091327