The unfolded protein response: An emerging therapeutic target for pancreatitis and pancreatic ductal adenocarcinoma

Investigating the Role of 17-Beta Estradiol in the Regulation of the Unfolded Protein Response (UPR) in Pancreatic Beta Cells

“…To further investigate the role of estrogen in alleviating protein misfolding and confirm the role of Pdi observed in our animal and cell experiments, further analysis using computer assisted molecular modeling methods, biophysical techniques such as thioflavin (ThT) fluorescence, or nuclear magnetic resonance spectroscopy (NMR), could shed more light on the process of protein misfolding in diabetes and how estradiol can modulate the UPR to alleviate this condition [29][30][31][32]. These techniques could provide more information on the effects of estrogen by measuring endoplasmic reticulum stress in real time in the case of ThT fluorescence and characterize possible interactions and potential alterations in protein structure as is the case of NMR [29][30][31][32].…”

Targeting extracellular CIRP with an X-aptamer shows therapeutic potential in acute pancreatitis

“… 25 , 26 Excessive ER stress can induce cell death and initiate inflammation. 27 Strategies of maintaining mitochondrial function and inhibiting excessive ER stress are the basis of many treatment approaches of AP. 26 , 28 , 29 , 30 , 31 Several studies have demonstrated that the TLR4 signaling pathway is involved in the regulation of mitochondrial and ER functions.…”

PGM3 inhibition Shows cooperative Effects With Erastin inducing Pancreatic cancer cell death via activation of the Unfolded Protein Response

“…Furthermore, we show that this combined treatment induces Unfolded Protein Response (UPR), NFE2 Like BZIP Transcription Factor 2 (NRF2) activation, a change in cellular redox state, a greater sensitivity to oxidative stress, a major dependence on glutamine metabolism, and finally ferroptosis cell death. Our study discloses that HBP inhibition enhances, through UPR activation, the ERA effect and therefore might be a novel anticancer mechanism to be exploited as PDAC therapy.chemoresistance, or it is an apoptotic inducer when prolonged in time (15). For this reason, some authors have suggested that targeting UPR in cancer including in PDAC may be highly beneficial, especially in combinatorial treatments that could provide an effective anti-tumorigenic response in patients.Therefore, in this study, we aimed to further detail the mechanism of FR054-induced cell death, in order to verify whether its pro-apoptotic ability could be enhanced by co-targeting a specific protein or cellular pathway.…”

“…chemoresistance, or it is an apoptotic inducer when prolonged in time (15). For this reason, some authors have suggested that targeting UPR in cancer including in PDAC may be highly beneficial, especially in combinatorial treatments that could provide an effective anti-tumorigenic response in patients.…”