TYRP1 Protects Against the Apoptosis and Oxidative Stress of Retinal Ganglion Cells by Binding to PMEL

Cracking the Code of Neuronal Cell Fate

“…Given the implication of core set genes in human pathology, our findings open the possibility to identify new or already existent therapeutics that are able to modulate their activity. To this regard, we performed a transcriptional signature connectivity analysis in iLINCS to explore repurposing drugs that could revert the expression of the core set genes during neuronal apoptosis, representing putatively therapeutically useful candidates [44]. iLINCS, in fact, also includes a comprehensive large-scale drug perturbation databases containing transcriptomic profiles of dozens of cultivated cell lines treated with thousands Given the implication of core set genes in human pathology, our findings open the possibility to identify new or already existent therapeutics that are able to modulate their activity.…”

“…Recently, we applied a "reverse engineering" method to identify candidate upstream regulators of early transcriptional changes observed following induction of CGNs apoptosis and its rescue by NFs [44]. In particular, we performed an in silico analysis to predict transcription factors (TFs) whose binding motifs are enriched in the promoter regions of core set genes [44].…”

“…Recently, we applied a "reverse engineering" method to identify candidate upstream regulators of early transcriptional changes observed following induction of CGNs apoptosis and its rescue by NFs [44]. In particular, we performed an in silico analysis to predict transcription factors (TFs) whose binding motifs are enriched in the promoter regions of core set genes [44]. Our analysis revealed that temporally distinct modules of core set genes are regulated by the coordinated action of nine TFs (Hoxd9, Maf, Nr4a1, Cebpb, Olig2, Onecut2, Spdef, Twist2, Nfyb) that may act as upstream regulators of neuronal cell fate, converging apoptosis and survival-inducing signals in a highly interconnected and temporally ordered manner (Figure 3) [44].…”

“…In particular, we performed an in silico analysis to predict transcription factors (TFs) whose binding motifs are enriched in the promoter regions of core set genes [44]. Our analysis revealed that temporally distinct modules of core set genes are regulated by the coordinated action of nine TFs (Hoxd9, Maf, Nr4a1, Cebpb, Olig2, Onecut2, Spdef, Twist2, Nfyb) that may act as upstream regulators of neuronal cell fate, converging apoptosis and survival-inducing signals in a highly interconnected and temporally ordered manner (Figure 3) [44]. In particular, these results showed a high degree of cross-regulation among the nine TFs as well as a common early (0.5 h and 1 h) and transient peak of transcription for the almost all TFs, with the exception of Onecut2 that was activated after 3 h following NF treatment (Figure 3).…”

“…In particular, these results showed a high degree of cross-regulation among the nine TFs as well as a common early (0.5 h and 1 h) and transient peak of transcription for the almost all TFs, with the exception of Onecut2 that was activated after 3 h following NF treatment (Figure 3). Of note, some of these transcription factors encode previously tested molecular/pharmacological targets and their exploitation may interfere with the early stages of the apoptotic/survival transcriptional program and represent novel therapeutic strategies [44]. In the following paragraphs, we will discuss these master regulators in light of their potential role as therapeutic targets for neurological disorders.…”