Microtubule defects in mesenchymal stromal cells distinguish patients with Progressive Supranuclear Palsy |
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Author: | Calogero, Alessandra Maria1; Viganò, Mariele2; Budelli, Silvia2; |
Organizations: |
1Department of Biosciences, Università degli Studi di Milano 2Department of Services and Preventive Medicine, Laboratory of Regenerative Medicine ‐ Cell Factory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico 3Department of Physiopathology and Transplantation, Dino Ferrari Center, Neurodegenerative Disease Unit, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, University of Milan
4Department of Surgery and Anatomy, Medical Research Center, University of Oulu and University of Oulu Hospital
5Parkinson Institute, ASST G.Pini‐CTO, ex ICP 6Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano |
Format: | article |
Version: | published version |
Access: | open |
Online Access: | PDF Full Text (PDF, 0.9 MB) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe2018060125152 |
Language: | English |
Published: |
John Wiley & Sons,
2018
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Publish Date: | 2018-06-01 |
Description: |
AbstractProgressive Supranuclear Palsy (PSP) is a rare neurodegenerative disease whose etiopathogenesis remains elusive. The intraneuronal accumulation of hyperphosphorylated Tau, a pivotal protein in regulating microtubules (MT), leads to include PSP into tauopathies. Pathological hallmarks are well known in neural cells but no word yet if PSP‐linked dysfunctions occur also in other cell types. We focused on bone marrow mesenchymal stromal cells (MSCs) that have recently gained attention for therapeutic interventions due to their anti‐inflammatory, antiapoptotic and trophic properties. Here, we aimed to investigate MSCs biology and to disclose if any disease‐linked defect occurs in this non‐neuronal compartment. First, we found that cells obtained from patients showed altered morphology and growth. Next, Western blotting analysis unravelled the imbalance in α‐tubulin post‐translational modifications and in MT stability. Interestingly, MT mass is significantly decreased in patient cells at baseline and differently changes overtime compared to controls, suggesting their inability to efficiently remodel MT cytoskeleton during ageing in culture. Thus, our results provide the first evidence that defects in MT regulation and stability occur and are detectable in a non‐neuronal compartment in patients with PSP. We suggest that MSCs could be a novel model system for unravelling cellular processes implicated in this neurodegenerative disorder. see all
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Series: |
Journal of cellular and molecular medicine |
ISSN: | 1582-1838 |
ISSN-E: | 1582-4934 |
ISSN-L: | 1582-1838 |
Volume: | 22 |
Issue: | 5 |
Pages: | 2670 - 2679 |
DOI: | 10.1111/jcmm.13545 |
OADOI: | https://oadoi.org/10.1111/jcmm.13545 |
Type of Publication: |
A1 Journal article – refereed |
Field of Science: |
3111 Biomedicine |
Subjects: | |
Funding: |
Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy, supported the research and the fellow to A.M.C. This work has also been supported by a research grant from Regione Lombardia—Independent Research, call 2012. |
Copyright information: |
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
https://creativecommons.org/licenses/by/4.0/ |