Microtubule defects in mesenchymal stromal cells distinguish patients with Progressive Supranuclear Palsy

Alessandra Maria Calogero, Mariele Viganò, Silvia Budelli, Daniela Galimberti, Chiara Fenoglio, Daniele Cartelli, Lorenza Lazzari, Petri Lehenkari, Margherita Canesi, Rosaria Giordano, Graziella Cappelletti, Gianni Pezzoli

Research output: Contribution to journalArticlepeer-review

Abstract

Progressive 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.

Original languageEnglish
Pages (from-to)2670-2679
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number5
DOIs
Publication statusPublished - May 1 2018

Keywords

  • bone marrow mesenchymal stromal cells
  • microtubules
  • neurodegeneration
  • Progressive Supranuclear Palsy

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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