中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (2): 234-235.doi: 10.4103/1673-5374.177723

• 观点:退行性病与再生 • 上一篇    下一篇

神经退行性变的合成生物学新发现:星形胶质细胞为治疗的新靶点

  

  • 收稿日期:2016-02-15 出版日期:2016-02-15 发布日期:2016-02-15

Synthetic cell pathobiology to study neurodegeneration: defining new therapeutic targets in astroglia

Matjaž Stenovec, Robert Zorec   

  1. Celica Biomedical, Ljubljana, Slovenia Laboratory of Neuroendocrinology-Molecular Cell Physiology,Institute of Pathophysiology, Faculty of Medicine, University of
    Ljubljana, Ljubljana, Slovenia
  • Received:2016-02-15 Online:2016-02-15 Published:2016-02-15
  • Contact: Robert Zorec, Ph.D., robert.zorec@mf.uni-lj.si.
  • Supported by:

    This work was supported by the Slovenian Research Agency grants P3 310, J3 3632, J3 4051, J3-4146, J3 6790, J3 7605. We thank Ms. Maja Ruper?i? and Mr. Mi?o Bo?i? for precious technical support.

摘要:

合成生物学是一门综合学科,意在以传统生物学获得的知识与材料为基础,利用系统生物学的手段对其加以定量的解析,在工程学以及计算机的指导下设计新的生物系统或对原有生物系统进行深度改造。斯洛文尼亚卢布尔雅那大学神经内分泌学-分子细胞生理学实验室Robert Zorec教授研究表明,在脱离了阿尔茨海默病病理环境下,实验用3xTg-阿尔茨海默病小鼠星形胶质细胞,第一次揭示了突变的早老素(PS1M146V) 的表达差异改变了不同囊泡类型的动态,这可能直接导致阿尔茨海默病的产生。Zorec教授认为,应用合成生物学方法,通过细胞重新编程技术重组出生后或成体成纤维细胞,诱导其成为星形胶质细胞,能为神经退行性疾病确定新的病例机制,并为以星形胶质细胞为靶点的神经退行性疾病治疗提供了新思路。

Abstract:

 Experiments on 3xTg-AD mouse astrocytes, devoid of their pathologic environment, revealed, for the first time, that the expression of mutated presenilin 1 (PS1M146V) differentially alters the dynamics of different vesicle types, which may contribute to the development of AD (Stenovec et al., 2016). The same experimental approach, however, is not possible in humans. Here, the use of iAstrocytes represents the major technological advancement and the only acceptable alternative to experimentally address the early dysfunction in cultured astroglial cells converted from fibroblast of diseased (and healthy) members of families with medical history of neurodegenerative diseases. Human iAstrocytes can be further used to develop a new diagnostic test based on analysis of vesicle mobility, which may aid predict the clinical manifestation of the disease already in the early, pre-symptomatic phase of disease. Thus, the synthetic pathobiology approach, where cell-reprogramming technology is used to convert embryonic, postnatal or adult fibroblasts, isolated from a patient, into induced astrocytes (iAstrocytes), appears to be a promising strategy to identify new mechanisms and targets in astroglia associated with neurodegeneration, such as AD.