Sacsin, a multidomain molecular chaperone involved in neurodegenerative disease

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Proteins are the essential biological molecules that build the machines which make the body function. Proteins must be folded into complex three dimensional shapes to work properly. Proteins that do not fold correctly are detected by ‘quality-control’ systems and are then disposed of by being degraded. This folding and controlled destruction of proteins involves a special group of proteins known as molecular chaperones. This work is focused on sacsin, a novel protein, which is able to regulate a molecular chaperone machine. Sacsin has an important role in the brain as mutations in its gene cause an inherited neuronal disease. To find out more about the biology of molecular chaperones and understand why mutations in sacsin cause disease we are investigating its precise function in cells. Sacsin’s function is being looked at through a comprehensive series of experiments. We are finding out where it’s located, what other proteins it interacts with and what happens when it’s absent. Studying sacsin is important because problems with protein folding lead to diseases where badly folded proteins accumulate; these include Alzheimer’s and Parkinson’s disease. What’s more molecular chaperones are associated with these conditions and in experimental models can slow disease progression.