Instead, 1 h of treatment with proNGF up-regulates DNA repair genes, both specific DNA polymerase involved in repair mechanisms and other single-strand and double-strand binding proteins that repair DNA breaks by recombination. As for the ����pure proNGF���� set, many genes involved in carbohydrate- as well as in lipid-metabolism were found to be significantly down-regulated. Interestingly, it has been recently shown that proNGF is modified by non-enzymatic glycation and lipidation in AD , although we cannot directly compare these modifications with the regulation by proNGF of carbohydrate and lipid post-translationally modifying enzymes, highlighted in PC12 cells. We then analyzed the genes specific for LY2109761 citations proNGF-WT and proNGF-KR, represented in the Venn diagrams by the orange and blue colours, respectively. The two proNGF-WT and -KR specific datasets contain different number of genes and different gene classes, suggesting that these two proteins behave somewhat differently. Since the two proNGF �CWT and �CKR proteins have been widely used interchangeably and functional differences among them have not been reported, we ascribe the transcriptional differences highlighted in this analysis to their differential processing during the incubation with PC12 cells, and hence to a distinct contribution by mature NGF in the two conditions. The results underscore the importance of the relative amount of NGF versus proNGF in the biological outcome. It appears therefore critical, when taking into account the signalling fingerprinting of proNGF, to consider both the amount of mature and precursor protein, particularly for in vivo situations. One gene family significantly modulated in the two treatments at 4 h is linked to synaptic functions and activity , although in the case of proNGF-WT, these genes are all down-regulated, while in the case of proNGF-KR they do not have a buy TH-302 homogeneous trend, being partly up- and partly down-regulated. Finally, the expression trend of specific genes, known to be linked to NGF and proNGF activity, were sought and analyzed in the different datasets. We could identify furin to be down-regulated in ����pure proNGF���� set, suggesting a feedback regulation loop possibly fine-tuning and reinforcing proNGF activity, by reducing its metabolism. Significantly, in the proNGF-WT at 1 h, the TrkA receptor gene is down regulated, further suggesting a feedback effect of proNGF-WT, leading to a reduced efficacy of signal transduction mediated by TrkA receptor. Despite the evidence of the cross-talk between the p75NTR and sortilin in the cell death induced by proNGF, we could not find a modulation in these receptors�� genes in the proNGF treatments.