Neuroprotective effects of mesenchymal stem cells through autophagy modulation in a parkinsonian model

作者：Park Hyun Jung; Shin Jin Young; Kim Ha Na; Oh Se Hee; Lee Phil Hyu^*

来源：Neurobiology of Aging, 2014, 35(8): 1920-1928.

DOI：10.1016/j.neurobiolaging.2014.01.028

• Mesenchymal stem cells
• Parkinson's disease
• Autophagy
• Autophagolysosome formation
• alpha-Synuclein

Autophagy is a major degradation pathway for abnormal aggregated proteins and organelles that cause various neurodegenerative diseases. Current evidence suggests a central role for autophagy in pathogenesis of Parkinson's disease, and that dysfunction in the autophagic system may lead to alpha-synuclein accumulation. In the present study, we investigated whether mesenchymal stem cells (MSCs) would enhance autophagy and thus exert a neuroprotective effect through the modulation of alpha-synuclein in parkinsonian models. In MPP+-treated neuronal cells, coculture with MSCs increased cellular viability, attenuated expression of alpha-synuclein, and enhanced the number of LC3-II-positive autophagosomes compared with cells treated with MPP+ only. In an MPTP-treated animal model of Parkinson's disease, MSC administration significantly increased final maturation of late autophagic vacuoles, fusion with lysosomes. Moreover, MSC administration significantly reduced the level of alpha-synuclein in dopaminergic neurons, which was elevated in MPTP-treated mice. These results suggest that MSC treatment significantly enhances autophagolysosome formation and may modulate alpha-synuclein expression in parkinsonian models, which may lead to increased neuronal survival in the presence of neurotoxins.

• 出版日期2014-8