Table 1.
Proteins involved in the development and progression of PD and MSC-derived factors responsible for the beneficial effects of MSC-EVs in the attenuation of PD.
| Molecule(s) | Cell Source | Effect(s) | Ref. No. |
|---|---|---|---|
| Altered LRRK2 kinase | Dopaminergic neurons | Impaired release of dopamine | [3,4] |
| Altered SNCA protein | Dopaminergic neurons | Increased aggregation of αSN | [3,4] |
| Altered PARK7 protein | Dopaminergic neurons | Mitochondrial dysfunction | [4,5] |
| Altered PINK1 kinase | Dopaminergic neurons | Disruption of mitochondrial homeostasis | [4,5] |
| Altered PRKN ligase | Dopaminergic neurons | Impaired proteasome-dependent degradation of altered proteins | [4,5] |
| TNF-α, IL-1β | Microglia | Increased expression of E and P selectins on ECs; increased permeability of BBB | [7] |
| IFN-γ, IL-17 | Th1, Th17 cells | Activation of microglia and brain-infiltrated neutrophils; progression of neuroinflammation | [9] |
| CD9, CD63, CD81 | MSCs | Increased uptake of MSC-EVs by target cells | [22] |
| IL-10, TGF-β | MSCs | Induction of tolerogenic phenotype in DCs; alternative activation of macrophages | [22,23] |
| IL-1Ra | MSCs | Suppression of IL-1β-driven neuroinflammation | [22,23] |
| IDO | MSCs | Increased generation and expansion of immunosuppressive Tregs | [23] |
| HGF | MSCs | Suppression of microglia | [23,24] |
| miR-133b, miR-21, miR-124 | MSCs | Promote resilience of dopaminergic neurons | [23,24] |
| BDNF, NGF, GDNF | MSCs | Support growth and survival of dopaminergic neurons | [23,24,25] |
| SOD, catalase | MSCs | Attenuation of oxidative stress-induced injury of dopaminergic neurons | [24,25] |
| TSG-6 | MSCs | Suppression of oxidative stress and attenuation of neurotoxicity | [37] |
Abbreviations: synuclein alpha (SNCA); leucine-rich repeat kinase 2 (LRRK2); parkinsonism associated deglycase (PARK7); α-synuclein (αSN); phosphatase and tensin-homolog (PTEN)-induced kinase 1 (PINK1); parkin RBR E3 ubiquitin protein ligase (PRKN); tumor necrosis factor-alpha (TNF-α); interleukin (IL)-1β; endothelial cell (EC); blood-brain barrier (BBB); interferon gamma (IFN-γ); mesenchymal stem cells (MSCs); mesenchymal stem cell-derived extracellular vesicles (MSC-EVs); transforming growth factor beta (TGF-β); interleukin 1 receptor antagonist (IL-1Ra}; indoleamine 2,3-dioxygenase (IDO); T regulatory cells (Tregs); hepatocyte growth factor (HGF); micro RNA (miR); brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF); glial cell line-derived neurotrophic factor (GDNF); superoxide dismutase (SOD); TNF-stimulated gene-6 (TSG-6).