The chaperone Grp78 in protein folding disorders of the nervous system

Chaperones are essential for the proper folding of proteins, and their dysfunction or depletion may be a key factor in protein folding disorders in the central nervous system. In normal conditions the cell regulates the proper folding of proteins by endoplasmic reticulum chaperones, called heat shock proteins, the cellular machinery that correctly folds newly synthesized and partially folded proteins or initiates degradation of misfolded proteins. Maintaining protein homeostasis within the cell is vital for the cells to function and survive. However, under conditions of cellular stress, proteastatic mechanisms must be activated to recycle, refold, or initiate degradation of misfolded or unfolded proteins. In this commentary, we will discuss the importance of chaperones, more specifically the 78 kd glucose regulated protein Grp78 (also known as BiP and HSP5a), in Parkinson's, Alzheimer's, Huntington's, and prion diseases, and the role that metals may play in exacerbating neurodegenerative diseases.