Emerging roles of peroxisome proliferator-activated receptors (PPARs) in the regulation of neural stem cells proliferation and differentiation.

The molecular mechanisms controlling the specification of neural cell fates have been the focus of intense research in recent years. Neural precursor cells (NPCs) sequentially undergo expansion, neurogenic and gliogenic fates during development, but the underlying mechanisms are poorly understood. Recent studies have identified a number of extrinsic factors that regulate the fate of NPCs. Wnt signaling induces neuronal differentiation of NPCs in an instructive manner. Wnt plays this role in the neurogenic phase of NPCs but not in the early expansion phase, when this pathway promotes proliferation. Likewise, STAT3-activating ligands induce astrocytic differentiation in late gliogenic phase of NPCs but not in the early expansion and neurogenic phases. The mechanisms underlying these remarkable changes in progenitor behaviour and fate during development are not understood, but are thought to include changes in the intrinsic properties of neural progenitors, as well as changes in their signalling environment. PPARs are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily, which activate the transcription of their target genes as heterodimers with retinoid X receptors (RXR). PPARs have been recently involved in NSC acquisition of a specific fate. They have been described to be involved in pathways present also in the control of the proliferation, migration and differentiation of NSC, i.e. Wnt signalling pathway, STAT3 and NFkB pathways. In this review the findings related to PPARs and NSC are reported as well as their possible linkage to other signal transduction pathways involved in NSC specification.