Mesenchymal stem cells and its derived matrix metalloproteinase-2 enhance degradation of extracellular α-synuclein aggregates in parkinsonian models

Abstract

Ample evidence has suggested that extracellular α-synuclein aggregates would play key roles in the pathogenesis and progression of Parkinsonian disorders (PD). In the present study, I investigated whether mesenchymal stem cells (MSCs) and their derived soluble factors could exert neuroprotective effects via proteolysis of extracellular α-synuclein. When preformed α-synuclein aggregates were incubated with MSC-conditioned medium, α-synuclein aggregates were disassembled and insoluble and oligomeric forms of α-synuclein were markedly decreased, thus leading to a significant increase in neuronal viability. In an animal study, MSC or MSC-conditioned medium treatment decreased the expression of α-synuclein oligomers and the induction of pathogenic α-synuclein with an attenuation of apoptotic cell death signaling. Furthermore, this study was identified that matrix metalloproteinase-2 (MMP-2), a soluble factor derived from MSCs, played an important role in the degradation of extracellular α-synuclein. this study was demonstrated that MSC and its derived MMP-2 exert neuroprotective properties through proteolysis of aggregated α-synuclein in PD-related microenvironments.