Affiliations: [a] Department of Biochemical Sciences, and Research Centre on the Molecular Basis of Neurodegeneration (CIMN), Florence, Italy | [b] Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy | [c] Department of Haematology, Ospedale di Careggi, Florence, Italy
Correspondence:
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Correspondence to: Cristina Cecchi, Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. Tel: +39 (055) 4598320; Fax: +39 (055) 4598905; E-mail: cristina.cecchi@unifi.it.
Note: [1] These authors contributed equally to this work.
Abstract: Cell therapy is a promising approach for the treatment of neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. However, the presence of toxic aggregates in tissue raises the question of whether grafted stem cells are susceptible to amyloid toxicity before they differentiate into mature neurons. To address this question, we investigated the relative vulnerability of human mesenchymal stromal cells and their neuronally differentiated counterparts to Aβ42 oligomers and whether susceptibility correlates with membrane GM1 content, a key player in oligomer toxicity. We found that our cell model was highly susceptible to aggregate toxicity, whereas neuronal differentiation induced resistance to amyloid species. This data correlated well with the content of membrane GM1, levels of which decreased considerably in differentiated cells. These findings extend our knowledge of stem cell vulnerability to amyloid species, which remains a controversial issue, and confirm that amyloid-GM1 interactions play an important role in cell impairment.
