The Protein Folding Toolkit
As our population ages, the prevalence of neurodegenerative disorders, such as Alzheimer's and Parkinson's, is expected to grow. Alzheimer's alone affects close to one percent of Canadians.
In human cells, many neurodegenerative disorders are characterized by abnormal protein aggregates. Normally, proteins do not aggregate. They are made up of long linear molecules called "polypeptides," which are folded into a stable structure (known as the "native state") - much like a single wire can be bent into a coiled spring or a clothes hanger. Failures in protein folding can lead to misfolding of polypeptides, and eventually to insoluble aggregates. like tangles of wires that cannot be unravelled.
Fortunately, cells have a protein folding toolkit consisting of "molecular chaperones"; they help proteins fold into their correct native states. Canada Research Chair Dr. Jason Young is particularly interested in two molecular chaperones, Hsp70 and Hsp90, which together handle a wide range of polypeptides. Numerous cofactor proteins, cellular defences against protein misfolding, control the action of these chaperones like switches, or act as adaptors to connect the chaperones with other cellular structures. Dr. Young's research focuses on how the chaperones and cofactors work together inside cells.
Certain cofactors recruit Hsp70 and Hsp90, not simply for protein folding, but also to move polypeptides around the cell, to make structural changes in already folded proteins, and even to sort out misfolded proteins for destruction. Dr. Young is investigating how the same chaperones can be used for such divergent purposes, and he is examining the many cofactors with still unknown functions. Drugs that support the chaperones and cofactors may eventually turn out to be the key to preventing the fatal consequences of protein aggregation.