Reclamation of proteins from the cellular scrap heap.
A growing number of diseases have been associated with protein misfolding. Thus, strategies that use small molecules to adjust folding tendencies have therapeutic potential. However, progress in this area has been hampered by an insufficient description of the molecular underpinnings of protein instability within the cell. In a recent report, a chemical approach was taken to probe the mechanism by which Gaucher disease associated mutations in glucocerebrosidase destabilize that enzyme and lead to its destruction. These studies provide a blueprint for the design of "chemical chaperones" for the exploration of cellular protein homeostasis and the treatment of misfolding diseases.
Gestwicki
Jason E
JE
Department of Pathology and the Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109-2216, USA. gestwick@umich.edu
D000818:Animals; D005776:Gaucher Disease / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
D018832:Molecular Chaperones; D011506:Proteins