Another common theme emerging from these and other studies is that axon

regeneration involves transcriptional and posttranscriptional regulation. The MLN0128 main Notch effector NICD localizes to the nucleus of injured GABAergic neurons, and the constitutive expression of NICD potently inhibits their commissural axon regeneration (El Bejjani and Hammarlund, 2012). In PLM neurons, DLK-1-mediated regrowth requires a bZip transcription factor CEBP-1 and its local translation at the severed site (Yan et al., 2009). In Drosophila neurons, DLK-mediated regeneration involves the Fos transcription factor ( Xiong et al., 2010). Additional transcription factors, as well as regulators of chromatin remodeling

and mRNA metabolism, influence PLM axon regeneration ( Chen et al., 2011). These observations indicate that local and nuclear gene regulatory responses may contribute to different phases of regeneration. It will be important to identify and compare the downstream target(s) of these regulatory proteins. As demonstrated in these two recent studies, the repertoire of C. elegans genetic mutants allows for both genome-wide screens and targeted investigation of factors that positively and negatively regulate axon regeneration. The factors and genetic pathways identified by 3-Methyladenine these studies, however, probably represent only the tip of the iceberg. Recently identified intrinsic inhibitors for adult mouse retinal ganglion cell axon regeneration include more transcriptional regulators, such as the Krüppel-like factors, repressors of mTOR-mediated protein translation PTEN and TSC1, as well as SOCS3, a negative regulator of JAK/STAT signaling (reviewed in Liu et al., 2011). The dual deletion

of PTEN and SOCS3 results in significantly more sustained axon regeneration than either single gene deletion ( Sun et al., 2011), further supporting the view that the interplay of multiple regeneration-promoting factors determines the regenerative Rebamipide ability of neurons. Given that the cellular response to injuries inflicted by various forms of axotomy and neurological trauma may differ, assessing the effect of multiple factors in different neurons, injury paradigms, and animal models is critical for revealing general and specific targets for nervous system repair. Results from Chen et al. (2011) and El Bejjani and Hammarlund (2012) provide exciting starting points for testing the role of orthologous proteins in other animal and injury models for axon regeneration. “
“Over the past few decades it has become apparent that plasma membrane receptors can cooperatively signal as homo- and heteroligomers.