You are hereAugust 20, 2017 | Mesenchymal Stem Cells
MSC-treatment of Parkinson’s Disease: A New Mechanism Uncovered!
Review of “Mesenchymal stem cells stabilize axonal transports for autophagic clearance of α-synuclein in parkinsonian models” from STEM CELLS by Stuart P. Atkinson
Multiple studies from the laboratory of Phil Hyu Lee (Yonsei University College of Medicine, Seoul, South Korea) have demonstrated that mesenchymal stem cells (MSCs) represent a potentially exciting treatment option for the neurodegenerative disorder Parkinson’s disease (PD). Their new STEM CELLS study now evaluates a new means by which MSCs may protect against early PD development: the protection against axonal transport defects leading to enhanced neural cell survival .
The rationale for this new article “stems” from studies into the causes of PD, which have identified the α-synuclein (SNCA) synaptic protein and the microtubule (MT)-associated protein (MAP) tau as common risk factors [2-4]. Axonal defects lead to the abnormal accumulation of α-synuclein, which destabilizes microtubules (MT) via tau phosphorylation, so causing the nigral dopaminergic cell loss associated with PD .
The authors employed two model systems; human neuroblastoma cells (SH-SY5Y) overexpressing α-Synuclein and C57BL/6 mice injected with α-synuclein in the substantia nigra (SN). Encouragingly, coculture or systemic injection of human MSCs reversed the unwanted α-synuclein-mediated disruptions to MT networks and trafficking and this promoted neuronal protection and survival.
In-depth analysis indicated that MSCs secreted the eukaryotic elongation factor 1A-2 (EEF1A2) protein, which stabilized MT assembly, so enhancing the movement of cell substituents between the neural cell body and the axons. The increased levels of MT-dependent trafficking subsequently permitted the clearance/degradation of unwanted of α-synuclein aggregates via the fusion of autophagosomes with late endosomes/lysosomes. The reduction in α-synuclein then reduced calcium/calmodulin-dependent phosphorylation of the tau protein, which in turn enhanced the survival of dopaminergic neurons.
In conclusion, this intriguing new study suggests that pharmacological manipulation of MT assembly or axonal transport may represent a means to treat α-synuclein related disorders, such as PD.
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- Oh SH, Lee SC, Kim DY, et al. Mesenchymal Stem Cells Stabilize Axonal Transports for Autophagic Clearance of α-Synuclein in Parkinsonian Models. STEM CELLS 2017;35:1934-1947.
- Edwards TL, Scott WK, Almonte C, et al. Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Annals of human genetics 2010;74:97-109.
- Mata IF, Yearout D, Alvarez V, et al. Replication of MAPT and SNCA, but not PARK16-18, as susceptibility genes for Parkinson's disease. Mov Disord 2011;26:819-823.
- Simon-Sanchez J, Schulte C, Bras JM, et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet 2009;41:1308-1312.
- Chu Y, Morfini GA, Langhamer LB, et al. Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease. Brain 2012;135:2058-2073.