The emerging understanding of the role of eNSCs in the adult mammalian brain suggested the relevance of these cells to disease. To address this issue, experiments were performed where the activation of eNSCs was induced in models of disease. This allowed the study of the consequences of activating eNSCs in the diseased brain. Several lines of evidence implicate the STAT3-Ser/Hes3 signaling axis in various diseases:
:* Activation of the signaling pathway by Delta4 in combination with basic fibroblast growth factor (bFGF) induces motor and sensory skill improvements in adult rat models of ischemic stroke (PMCAO model).
:* This signaling pathway may mediate pro-survival functions of macrophage migration inhibitory factor on neural stem cells.
:* Activation of the signaling pathway by Delta4, Angiopoietin 2, insulin, or a combination of the three and a JAK inhibitor induces motor skill improvements in adult rat models of Parkinson's disease (6-hydroxydopamine model).
:* RNA interference (“knockdown”) of Hes3 in cultures of cells with cancer stem cell properties from patients with glioblastoma multiforme reduces cell number.
:* Mice lacking Hes3 exhibit increased sensitivity to particular paradigms of pancreatic islet damage, suggesting roles in diabetes.