The current focus of researchers is to create certain types of cells in vitroas transplantation materials. The problem of this approach is that terminally differentiated cells may not integrate into the host. To overcome this problem, we may want to transplant premature cells, which can migrate and differentiate due to environmental cues received from the host, allowing for intrinsic proper functioning of the cells. Thus, we have to consider the effects that the pathological environment might have on the transplanted cells. Here, we show the effects of amyloid precursor protein and reelin on neural stem cell (NSC) differentiation, and demonstrate how we have regulated this effect to produce desirable cells under pathological conditions. We found that amyloid precursor protein increases glial differentiation via the notch and cytokine-signaling pathway, while reelin induces radial glial differentiation followed by neuronal differentiation via increasing phosphorylation of adapter protein disabled-1. Since amyloid and reelin are found in plaques within Alzheimer's disease, these findings may closely associate with NSC biology in the context of its pathology. By regulating these factors in Alzheimer's disease, we may be able to not only guide differentiation of transplanted NSCs, but also to modify progression of disease by guiding differentiation of endogenous NSCs.
Copyright 2010 S. Karger AG, Basel.