Endoplasmic Reticulum Stress, a Target for Drug Design and Drug Resistance in Parasitosis

Abstract

Endoplasmic reticulum stress (ER stress) can be induced when cellular protein homeostasis is damaged, and cells can activate the unfolded protein response (UPR) to restore protein homeostasis or induce cell death to facilitate the survival of the whole system. Globally, parasites are a constant threat to human health and are therefore considered a serious public health problem. Parasitic infection can cause ER stress in host cells, and parasites also possess part or all of the UPR under ER stress conditions. In this review, we aim to clarify the role of ER stress pathways and related molecules in parasites for their survival and development, the pathogenesis of parasitosis in hosts, and the artemisinin resistance of Plasmodium, which provides some potential drug design targets to inhibit survival of parasites, relieves pathological damage of parasitosis, and solves the problem of artemisinin resistance.

Salicin modifies osteoarthritis progression by binding on IRE1α and inhibiting IRE1α mediated endoplasmic reticulum stress

“…In current study, we obtained similar results by detecting cartilage matrix degeneration and inflammatory markers. The ER is a multifunctional organelle, where protein folding occurs prior to transport to extracellular surface or to different intracellular sites [27][28][29][30] . Three ER transmembrane proteins mediated UPR, including IRE1, pancreatic endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) 28,29 .…”

“…The ER is a multifunctional organelle, where protein folding occurs prior to transport to extracellular surface or to different intracellular sites [27][28][29][30] . Three ER transmembrane proteins mediated UPR, including IRE1, pancreatic endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) 28,29 . Among them, IRE1 is the most conserved gene from yeast to human, and it has two subtypes: IRE1α and IRE1β.…”

“…Recently, ER stress regulators were identified as new drug targets for several diseases [27][28][29]46 . During the progression of OA, chondrocytes are responsible for the biogenesis and maintenance of cartilage ECM.…”

Recent Research in Cell Stress and Microbial Infection

“…Malaria can result in high oxidative stress in its naturally pathogenic process, either a direct result of Plasmodium infection of erythrocytes or a consequence of the host response to infection, along with ER stress [ 7 ]. ER stress has been found in other parasitic infections such as Trypanosoma or Toxoplasma [ 8 ]. In fungal infection, host oxidative stress, nitrosative stress, and responses of pathogenic fungi against these stresses to facilitate adaptation to the host have also been investigated [ 9 ].…”

“…The findings on the crosstalk of ER stress and the anti-viral activity came to a suggestion on using a combination of ER stress inhibitors and others to suppress the SARS-CoV-2 virus binding and replication in the target cells [ 3 , 13 ]. ER stress has also been suggested as a therapeutic target for relieving pathological damage of parasitosis [ 8 ]. In bacterial infection, ROS-based alternative antimicrobials targeting oxidative stress to mitigate the problem of antibiotic resistance have recently been suggested [ 14 ].…”