Potencjalne zastosowanie terapeutyczne inhibitorów PERK
2019
Recent studies aimed at understanding the molecular mechanisms of human disease indicate that in the pathogenesis of many metabolic disorders, including inflammatory processes, aging of the organism, as well as cancer and neurodegenerative disorders, ER stress plays a significant role that is associated with the accumulation of misfolded proteins in the ER lumen. In response to ER stress, the UPR pathway, that has a dualistic role, is induced. The UPR can restore ER homeostasis by degradation of unfolded proteins, inhibition of translation, and mobilization of chaperons, but it can also promote apoptosis when ER stress is prolonged. The UPR signaling pathways may be activated via three transmembrane receptors such as: PERK, IRE1 and ATF6. The most promising for development of new therapies of many human diseases, in particular cancer and neurodegeneration is PERK pathway, that inhibition shows positive therapeutic effects both in in vitro and in vivo studies.
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