NF-κB contributes to 6-hydroxydopamine-induced apoptosis of nigral dopaminergic neurons through p53

p53 mediates mitochondria dysfunction-triggered autophagy activation and cell death in rat striatum

“…23,31 PFT is a small molecule which is capable of inhibiting p53 activity. 3-MA is a nucleotide derivative that blocks class III PI3K activity and has been widely used for identifying autophagy functions.…”

“…PFT is a p53 specific inhibitor and has been shown to inhibit p53 signaling and p53-mediated apoptosis. 30,31 The results showed that pretreatment with PFT significantly inhibited 3-NP-induced elevation in mRNA and protein levels of PUMA and BAX, indicating p53-mediated signaling was efficiently blocked (Fig. 6A-F).…”

Pathologies Associated with the p53 Response

“…PFTa was also shown to protect against neuron degeneration induced by 6-Hydroxydopamine (Biswas et al 2005;Liang et al 2007), proteasome inhibitors (Nair et al 2006), and the herbicide paraquat (a suspected etiologic factor in the development of Parkinson's disease) (Yang and Tiffany-Castiglioni 2008). Moreover, PFTa inhibited glutamate-and kainite (an analog of glutamate)-induced p53-mediated neuronal death (Morrison et al 1996;Xiang et al 1998;Liu and Zhu 1999;Culmsee et al 2001;Neema et al 2005) and protected mouse synaptosomes against excitotoxic injuries (Gilman et al 2003).…”

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

“…The NF-κB-dependent induction of p53 was also found in response to DNA damage and oxidative stress. The induced p53 was apparently involved in cell death under these conditions as the synthetic p53 inhibitor pifithrin-α blocked neuronal apoptosis [42][43][44][45] . NF-κB not only regulates the levels of p53, but also increases the stability of the DNA binding of p53, providing an additional mechanism for promoting p53-mediated pro-apoptotic signaling [46] .…”