Department of Biochemical Sciences, and Research Centre on the Molecular Basis of Neurodegeneration (CIMN), Florence, Italy.
J Alzheimers Dis. 2011;27(3):651-64. doi: 10.3233/JAD-2011-110590.
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 Aβ(42) 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.
细胞疗法是治疗阿尔茨海默病和帕金森病等神经退行性疾病的一种很有前途的方法。然而，组织中存在有毒的聚集物引发了这样一个问题，即在分化为成熟神经元之前，移植的干细胞是否容易受到淀粉样蛋白毒性的影响。为了解决这个问题，我们研究了人基质干细胞及其神经分化对应物对 Aβ（42）寡聚物的相对易感性，以及易感性是否与膜 GM1 含量相关，GM1 是寡聚物毒性的关键因素。我们发现我们的细胞模型对聚集物毒性非常敏感，而神经元分化诱导对淀粉样蛋白物质的抗性。这一数据与膜 GM1 的含量很好地相关，而分化细胞中的 GM1 水平则大大降低。这些发现扩展了我们对干细胞对淀粉样蛋白物质易感性的认识，这仍然是一个有争议的问题，并证实了淀粉样蛋白 - GM1 相互作用在细胞损伤中起着重要作用。
