Researchers in the University of Iowa Roy J. and Lucille A. Carver College of Medicine have identified a protein, called CHIP (C-terminal heat shock protein 70-interacting protein), that links two arms of the quality-control machinery: refolding of misshapen proteins and destruction of proteins that are damaged beyond repair.
"For all kinds of neurodegenerative disease, from Alzheimer's disease to Huntington's disease -- which was the focus of our study -- there are problems with protein folding and protein handling," said Henry Paulson, M.D., Ph.D., UI associate professor of neurology and senior author of the study. "The protein CHIP is a key player in that process. Understanding and manipulating this pathway could lead to therapies for these diseases."
Huntington's disease is a devastating, inherited, neurodegenerative disease that is progressive and always fatal. The disease-causing gene produces a protein that is toxic to certain brain cells, and the subsequent neuronal damage leads to movement disorders, psychiatric disturbances and cognitive decline. The mutated protein contains an abnormally long stretch of a repeated amino acid and is prone to misfold and clump together, forming aggregates.
Working with several models of Huntington's disease (HD), Paulson and his colleagues found that CHIP could suppress the disease. The study, published in the Oct. 5 issue of the Journal of Neuroscience, demonstrated that CHIP decreased aggregation of the mutant protein and cell death in mouse neurons and in zebrafish. The UI team also found that in mice with only one copy of the CHIP gene, genetically engineered HD progressed
Contact: Jennifer Brown
University of Iowa