Mesenchymal stem cells modulate misfolded α-synuclein in parkinsonian disorders: A multitarget disease-modifying strategy

Stem Cell Research
Jin Young Shin, Phil Hyu Lee

Abstract

α-Synuclein (α-Syn) aggregates, the major toxic component of Lewy bodies, are proteinaceous fibrillar cytoplasmic inclusions observed in α-synucleinopathies, such as Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy bodies. Overexpression of α-syn induce neuronal loss and α-syn aggregation in PD animals. Recent studies show that α-syn is released by exocytosis and can be transmitted between brain areas through cell-to-cell propagation. Moreover, aggregates of extracellular α-syn can induce neuroinflammation-mediated neurotoxic signaling through microglial activation and release of pro-inflammatory factors. Thus, modulation of α-syn might be a potential therapeutic strategy for modifying disease progression of α-synucleinopathies. Our previous studies have revealed that MSCs have potent neuroprotective effects in PD animal through modulation of neuroinflammation, inhibition of cell death, and promotion of neurogenesis. Here, we provide further evidence that MSCs have the potential to modulate α-syn-related microenvironments via enhancement of autophagy, proteolysis of α-syn aggregates, inhibition of cell-to-cell transmission of α-syn, stabilization of axonal transport, and phagocytic clearance of α-syn by...Continue Reading

Citations

Jan 30, 2021·Neural Regeneration Research·Sachchida Nand RaiBrijesh Kumar Singh
Mar 4, 2021·International Journal of Molecular Sciences·Mahesh RamalingamHan-Seong Jeong
Aug 21, 2021·Frontiers in Cell and Developmental Biology·Shanshan ChenDi Wang

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