Mitochondrial dysfunction in Parkinsonian mesenchymal stem cells impairs differentiation

Redox Biology
Plamena R AngelovaLorenza Lazzari

Abstract

Sporadic cases account for 90-95% of all patients with Parkinson's Disease (PD). Atypical Parkinsonism comprises approximately 20% of all patients with parkinsonism. Progressive Supranuclear Palsy (PSP) belongs to the atypical parkinsonian diseases and is histopathologically classified as a tauopathy. Here, we report that mesenchymal stem cells (MSCs) derived from the bone marrow of patients with PSP exhibit mitochondrial dysfunction in the form of decreased membrane potential and inhibited NADH-dependent respiration. Furthermore, mitochondrial dysfunction in PSP-MSCs led to a significant increase in mitochondrial ROS generation and oxidative stress, which resulted in decrease of major cellular antioxidant GSH. Additionally, higher basal rate of mitochondrial degradation and lower levels of biogenesis were found in PSP-MSCs, together leading to a reduction in mitochondrial mass. This phenotype was biologically relevant to MSC stemness properties, as it heavily impaired their differentiation into adipocytes, which mostly rely on mitochondrial metabolism for their bioenergetic demand. The defect in adipogenic differentiation was detected as a significant impairment of intracellular lipid droplet formation in PSP-MSCs. This result...Continue Reading

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Citations

Jan 3, 2018·FEBS Letters·Plamena R Angelova, Andrey Y Abramov
Mar 5, 2018·Journal of Cellular and Molecular Medicine·Alessandra Maria CalogeroGianni Pezzoli
Aug 1, 2018·Stem Cells Translational Medicine·Juliana RedondoClaire M Rice
Jun 20, 2019·Journal of Cellular Physiology·Xiuling ShangRongguo Yu
Dec 21, 2019·Journal of Receptor and Signal Transduction Research·Yang YangZhiyun Wang
Jan 29, 2020·Journal of Receptor and Signal Transduction Research·Peng LiQiuyun Tu
Jun 26, 2020·Journal of Receptor and Signal Transduction Research·David Mui, Ying Zhang
Jul 14, 2020·Medicinal Research Reviews·Plamena R AngelovaAndrey Y Abramov
Nov 27, 2019·Biochemical Society Transactions·Andrey Y Abramov, Plamena R Angelova
Aug 30, 2019·Journal of Receptor and Signal Transduction Research·Long BaoZhixiong Lin
Aug 3, 2019·International Journal of Molecular Sciences·Francisco J VizosoRoman Perez-Fernandez
Oct 30, 2019·Journal of Receptor and Signal Transduction Research·Xinyu Song, Tianchang Li
Oct 30, 2019·Scientific Reports·Mario BarilaniLorenza Lazzari
Sep 30, 2018·Cellular and Molecular Life Sciences : CMLS·Prajna Paramita NaikSujit Kumar Bhutia
Oct 16, 2019·Journal of Cellular Physiology·Dezhi Huang, Yugang Jiang

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Methods Mentioned

BETA
confocal microscopy
electrophoresis
PCR

Clinical Trials Mentioned

NCT01824121

Software Mentioned

GraphPad
Andor
GraphPad Prism
Zeiss
Origin
REBORNE

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