Chaperoning Disease Treatment into the 21st Century

Chaperoning Disease Treatment into the 21st Century

Alvin Sherman Library 4009

Chaperones function as the cell’s quality control system in a number of different ways. Simply put they are protein complexes that help fold new proteins into their working form, refold proteins that have been damaged, protect against protein aggregation, and tag severely damaged proteins for degradation. Because they most notably respond to damaged proteins caused by cellular environmental stresses such as proteotoxic heat shock, they are often called heat-shock or stress proteins and are classified by their molecular size, cellular compartment and function (e.g. Hsp 90). The chaperones are ligand specific, cylindrical protein complexes that make life and death decisions about the ultimate fate of proteins. Through recognition of motifs, exposed hydrophobic regions, or ubiquitin tagged sequences, proteins leave the chaperone being properly folded, are sequestered by the cell, or they are disassembled by proteolytic active sites Interestingly, chaperones have the ability to overlook minor mutations in polypeptide chains before they are folded into higher level structures, which allows the protein to be able to function normally. The purpose of this literature research project is to investigate a novel approach to disease treatment, the targeting of chaperones. This paper will summarize what happens to the cell when the chaperone is overloaded with mutated proteins, oncogenic proteins are favored over normal ones, or the chaperone becomes too picky with regard to understanding origins and treating diseases as diverse as Alzheimer’s disease, cancer, and cystic fibrosis.