Huntington's and Parkinson's may have different pathologies

The respective proteins which cause Parkinson's disease and inherited forms of Huntington's disease are regulated by different sets of genes and cellular pathways, according to researchers at the UW and elsewhere. The findings, published in the Dec. 5 issue of Science, suggest that the two diseases may not share the same pathogenic mechanism and could require completely different approaches to developing treatments.

The study was led by Dr. Paul Muchowski, assistant professor of pharmacology at the UW, and co-authored by Dr. Susan Lindquist, director of the Whitehead Institute for Biomedical Research in Cambridge, Mass. The two research teams used yeast cells to examine the effects of the proteins that cause both Parkinson's and Huntington's.

Both alpha-synuclein, or aSyn, the protein linked to Parkinson's, and huntingtin, the protein that causes Huntington's, form clumps of aggregated protein in neurons. This protein accumulation, which is similar in both disorders, somehow leads to cell dysfunction and death. However, the researchers found that the proteins are regulated by completely different sets of genes: aSyn by those relating to lipid metabolism and membrane trafficking, and huntingtin by genes involved with protein folding and quality control.

The findings indicate that the diseases do not overlap at the molecular level and likely have different pathological mechanisms, and so will probably require different approaches to identify drugs to treat the disorders. The studies will also help guide future research into the causes of cell death in the disorders.