Visiting the ER: the endoplasmic reticulum as a target for therapeutics in traffic related diseases.
The endoplasmic reticulum (ER) is a central processor that controls the expression of functional proteins, required for the communication of the cell with the external environment. Plasma membranes receptors, ion channels, secreted hormones, catabolic and metabolic enzymes are folded and assembled in the ER. Key metabolic functions are also regulated from the ER. Molecular quality control monitors ER processing activities and co-ordinates these activities with cell and organism demands. Recent understandings of the molecular basis for ER processing activities illuminate the key role of the ER in the development of a variety of diseases. ER derived diseases include specific genetic disorders such as cystic fibrosis or highly prevalent diseases including diabetes and a range of neurodegenerative diseases. ER processing also plays a key role in the development of cancer. This review summarizes the molecular basis for ER processing functions and current avenues in ER-targeted drug development.
Aridor
Meir
M
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, 3500 Terrace St. Pittsburgh PA 15261, USA. aridor+@pitt.edu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D022181:COP-Coated Vesicles / Q000187:drug effects / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism; D018832:Molecular Chaperones / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D022161:Transport Vesicles / Q000187:drug effects
D018832:Molecular Chaperones; D018696:Neuroprotective Agents