The Role of TLR4 in Neural Stem Cells–Mediated Neurogenesis and Neuroinflammation

Stem cells in brain niches are responsible for neurogenesis and integration of new neurons into functional circuits, with inflammatory and immune system mediators playing critical roles in neurogenesis and in several diseases of the nervous system. TLR4 is known to be a master player in the development of neuroinflammation processes and to be upregulated in several animal models of neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). Nonetheless, Toll-like receptor 4 (TLR4) also plays a key role in CNS homeostasis. TLR4 is expressed in microglia, which is a master player in neuroinflammatory processes, as well as in neural cells: astrocytes, neurons, oligodendrocytes, neural progenitors (NPCs), and neural stem cells (NSCs). Here we discuss the dual role of TLR4 in brain homeostasis, suggesting that, in a translational perspective, TLR4-mediated regulation of human neural stem cells (hNSCs) needs to be deeply investigated either for the identification of novel biomarkers for rare diseases or future therapeutic approaches of aging and neurodegenerative disorders.