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.