Stem cell biology in the study of pathological conditions.
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.
Sugaya
K
K
College of Medicine, University of Central Florida, Orlando, FL, USA. ksugaya@mail.ucf.edu
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases