Table 2 multitarget disease-modifying therapies of MSCs modulates α-Syn in PD
Compound | Cell source | Mechanism | Study description and purpose |
|---|---|---|---|
Immunomodulation | Bone marrow | MSCs can promote the polarization of M2 phenotype microglia and reduce the aggregation of α-Syn in cortical areas by activating IL-4-related STAT signaling pathways | MSCs exert a neuroprotective effect via the clearance of extracellular α-synuclein by controlling microglia M2 polarization, suggesting that MSCs could be used as a disease-modifying therapy for patients with α-synucleinopathies |
Bone marrow | MSCs can modulate microglia activation through TSG-6 and that TSG-6 attenuates the inflammatory cascade in activated microglia | The immunomodulatory effect of MSCs on microglia and that MSCs might be promising therapeutic agents for the treatment of neurotraumatic injuries or neuroinflammatory diseases associated with microglial activation | |
Autophagy | Bone marrow | MSCs can exert neuroprotective effects through enhancement of autophagolysosome formation and modulation of a-synuclein expression, possibly via the autophagic pathway | The modulation of the autophagic pathway to control PD-related microenvironments using MSCs will have a significant impact on future PD treatment strategies |
Mediate endocytosis | Human MSCs (Obtained from the Severance Hospital Cell Therapy Center) | MSCs can block extracellular α-Syn clathrin-mediated endocytosis (CME) by regulating the interaction with n-methyl-d-aspartic acid (NMDA) receptors | MSCs can exert neuroprotective properties through inhibition of extracellular α-synuclein transmission, suggesting that the property of MSCs may act as a disease-modifying therapy in subjects with α-synucleinopathies |
Bioprotease | Human MSCs (Obtained from the Severance Hospital Cell Therapy Center) | MSCs secreted MMP-2 molecules can disrupt newly formed amyloid deposition, significantly reducing α-Syn insolubility and oligomeric levels | MSCs can exert neuroprotective properties through proteolysis of aggregated α‐synuclein into soluble forms, and have a significant impact on future PD treatment strategies |