Along with a circadian function, mPer1 gene expression may also have an important role when expressed in ultradian oscillations such as those observed in SCM neurospheres. These rhythms may be working with stem cell-maintaining genes such as the hes family that are expressed in ultradian oscillations during neurogenesis and embryogenesis where they play an important role in repressing genes used in differentiation. Neurogenesis and circadian oscillators both rely on a collection of basic-helix-loop-helix transcription factors, some of which are shared between these two time-dependent processes. For example, one gene promoter element used in circadian transcriptional control Axitinib inquirer includes the Nbox that binds the bHLH HES1 protein. The circadian clock could also have a direct effect on differentiation through its control of an E-box element of the Pax6 gene promoter. Pax6 serves in determining the rate and direction of neurogenesis in the OB. If circadian timing, rather than non-rhythmic clock gene expression, has a functional role in adult NSPCs during early stages of differentiation, circadian oscillations may modulate particular differentiation events. In a similar way, daily oscillations in brain cortisol appear to gate cell proliferation in adult mouse hippocampus. Again, coupling between circadian and stem cell-maintaining genes could serve in this control. Alternatively, neurogenesis and circadian timing processes could act independently within the same cells despite predicted interactions between the bHLH transcription factors acting on N-box and E-box elements. The SVZ neurosphere cultures examined here provide a useful assay to investigate the role of circadian clocks and clock-controlled genes in adult neurogenesis. Understanding the relationship between circadian clock genes and neurogenesis could provide new targets for more effective treatments and prevention of neurological disorders such as Parkinson��s and Alzheimer��s diseases that are suitable for stem cell therapies. If circadian timing acts on differentiation, then circadian expression patterns may be manipulated to induce NSPCs to differentiate more readily into specific cell types needed to compensate for neural deficits. Effective therapeutic targeting of Wallerian degeneration and other types of axon degeneration that share a common molecular basis could have profound implications for numerous neurodegenerative diseases where axonopathy contributes to pathogenesis. An aberrant fusion protein, WldS, naturally only found in a single mutant mouse, can delay Wallerian degeneration markedly. Studies of WldS function have provided considerable insight into the Dasatinib Src-bcr-Abl inhibitor intrinsic mechanisms involved in the process and have recently led to the identification of a number of key regulatory molecules and pathways. This includes the finding that NMNAT2, which shares critical nicotinamide mononucleotide adenylyltransferase activity with WldS, is an endogenous axon maintenance factor, with depletion of NMNAT2 in axons likely acting as a trigger for degeneration. Despite being predominantly nuclear, a small pool of axonal WldS appears to be responsible for protection. Consequently, because WldS is much more stable than very short-lived NMNAT2, it has been suggested that it delays axon degeneration by directly substituting for NMNAT2 loss in compromised axons. However, the relationship between NMNAT activity and other regulators and/or executers of the degeneration pathway has yet to be fully established. Canonical MEK1/2-ERK1/2 signaling, and more recently MEK5-ERK5 signaling, have been shown to be critical for neuronal stress responses and/or neurotrophin-mediated neuronal survival.