Akademik Veri Yönetim Sistemi
Fabad Journal of Pharmaceutical Sciences, cilt.33, sa.3, ss.163-176, 2008 (Scopus)
In cells, the quality of newly synthesized proteins is monitored with endoplasmic reticulum quality control (ERQC) in regard to proper folding and correct assembly in the early secretory pathway. Sequential checkpoints are distributed along the early secretory pathway, allowing efficiency and fidelity in protein secretion. Recently, ERQC has been mathematically modeled by breaking it into three subpathways; termed the Endoplasmic Reticulum Associated (ERA) Degradation (ERAD), ERA-Folding (ERAF) and ERA-Transport pathways. The major aim of ERQC is to assure that only properly folded and assembled proteins in the endoplasmic reticulum (ER) are transported for furher maturation and secretion. Disturbances in the ERQC have been linked with the pathophysiology of many human diseases; diabetes mellitus, alzheimer, parkinson, lysosomal storage diseases etc. Enzyme enhancement therapy, which uses pharmacological chaperones, is an emerging therapeutic approach that has the potential to treat many genetic diseases, associated with a mutant protein having difficulty in folding and/or assembling into active oligomers in the ER. This review focuses on the ERQC and its pathways, unfolded protein response in the ER, pharmacological chaperones and their action mechanisms.