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Mitochondrial dysfunction in Parkinsonian mesenchymal stem cells impairs differentiation

Angelova, PR; Barilani, M; Lovejoy, C; Dossena, M; Viganò, M; Seresini, A; Piga, D; ... Lazzari, L; + view all (2018) Mitochondrial dysfunction in Parkinsonian mesenchymal stem cells impairs differentiation. Redox Biology , 14 pp. 474-484. 10.1016/j.redox.2017.10.016. Green open access

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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 was corroborated at the transcriptional level by a significant reduction of PPARγ and FABP4 expression, two key genes involved in the adipogenic molecular network. Our findings in PSP-MSCs provide new insights into the etiology of 'idiopathic' parkinsonism, and confirm that mitochondrial dysfunction is important to the development of parkinsonism, independent of the type of the cell.

Type: Article
Title: Mitochondrial dysfunction in Parkinsonian mesenchymal stem cells impairs differentiation
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.redox.2017.10.016
Publisher version: https://doi.org/10.1016/j.redox.2017.10.016
Language: English
Additional information: Copyright © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Keywords: Mesenchymal stem cells, Parkinsonism, Progressive supranuclear palsy
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/10034568
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