Fig. 4

Mechanisms of MSC multitarget immunotherapy in PD. Through their paracrine effect, MSCs secrete a large number of immunomodulatory cytokines. MSCs can promote M2 phenotype microglia polarization and reduce α-Syn aggregation in cortical areas by activating IL-4-related STAT signaling pathways (1). MSCs can significantly increase the formation of LC3-positive autophagosomes and decrease α-Syn aggregation (2) by activating the autophagy signaling pathway. MSCs inhibit extracellular α-Syn CME by regulating clathrin and EEA1, as well as the interaction between α-Syn and nNMDA receptors by releasing Gal-1, which completely binds NMDA receptors with α-Syn (3, 4). MSCs can eliminate abnormal α-Syn expression and accelerate its degradation via secretory small molecule cleavage, such as MMP-2 (5). We hypothesized that hypoxia preconditioning MSCs would prevent pyroptosis in microglia cells by down-regulating the NLRP3 inflammasome via the HIF-1 signaling pathway (6). MSCs can significantly induce M2 phenotype microglia cell polarization and have a significant dopaminergic neuronal protective effect by attenuating inflammation amplification (7). MSCs can significantly induce M2 phenotype microglia cell polarization and have a significant dopaminergic neuronal protective effect by attenuating the antigen presentation process and T cell chemokine secretion (8)