Review: Protein misfolding diseases - the rare case of Marinesco-Sjögren syndrome.

摘要: Secretory and cell membrane proteins are synthesized in the endoplasmic reticulum (ER), where a network of molecular chaperones folding factors ensure correct protein export to post-ER compartments. Failure this process leads accumulation unfolded/misfolded proteins, ER stress, activation unfolded response (UPR), complex signalling pathway aimed at restoring homeostasis, whose failure eventually death. Suppressor Ire1/Lhs1 double mutant (SIL1) is nucleotide exchange factor for immunoglobulin binding protein, main chaperone primary sensor stress. Loss SIL1 function causes Marinesco-Sjogren syndrome (MSS), rare multisystem disease early infancy which there no cure. This review, examines current understanding activities ER, reviews experimental data describing consequences deficiency animal models. We discuss evidence supporting role UPR - particularly kinase RNA-like branch pathogenesis MSS, how may be pharmacologically manipulated treatment.