the unfolded protein response monitors protein folding in the ______, releasing signals into the ______ that increase the protein folding capacity of the er.?
The ability to monitor protein biomarkers continuously and in real-time would significantly advance the precision of medicine. Current protein-detection techniques, however, including ELISA and lateral flow assays, provide only time-delayed, single-time-point measurements, limiting their ability to guide prompt responses to rapidly evolving, life-threatening conditions. In response, here we present an electrochemical aptamer-based sensor (EAB) that supports high-frequency, real-time biomarker measurements. Specifically, we have developed an electrochemical, aptamer-based (EAB) sensor against Neutrophil Gelatinase-Associated Lipocalin (NGAL), a protein that, if present in urine at levels above a threshold value, is indicative of acute renal/kidney injury (AKI). When deployed inside a urinary catheter, the resulting reagentless, wash-free sensor supports real-time, high-frequency monitoring of clinically relevant NGAL concentrations over the course of hours. By providing an “early warning system”, the ability to measure levels of diagnostically relevant proteins such as NGAL in real-time could fundamentally change how we detect, monitor, and treat many important diseases.
the unfolded protein response monitors protein folding in the ______, releasing signals into the ______ that increase the protein folding capacity of the er.?
Denaturation of proteins is the reverse process, ie the transition from an folded to an unfolded state, and it occurs during cooking and burning in proteasomes and other contexts.
The duration of folding varies greatly depending on the protein. When the extracellular protein is studied, the slowest folding proteins need several minutes or hours to fold due to proline isomerism and must pass through intermediate states – such as checkpoints – before the process can take place. On the other hand, very small single-domain proteins of less than 100 amino acids in length usually fold in a single step. The time scale is in milliseconds and the fastest known protein folding reactions take place within a few microseconds.
The unfolded protein response (UPR) is a signal transduction network activated by inhibition of protein folding in the endoplasmic reticulum (ER). The UPR coordinates adaptive responses to this stress situation, including induction of ER resident molecular chaperone and protein foldase expression to increase the protein folding capacity of the ER, induction of phospholipid synthesis, attenuation of general translation, and upregulation of ER-associated degradation to decrease the unfolded protein load of the ER, and an antioxidant response. Upon severe or prolonged ER stress the UPR induces apoptosis to eliminate unhealthy cells from an organism or a population. In this review, I will summarize our current knowledge about signal transduction pathways involved in transducing the unfolded protein signal from the ER to the nucleus or the cytosol.