A novel method of disrupting abnormal protein deposits in the brain associated with neurodegenerative disease is presented in a study published online this week in Nature Chemical Biology.
Neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's are characterized by the presence of protein aggregates in the brain that are thought to be toxic. These aggregates arise from abnormal protein-protein interactions and are not only physically obtrusive, but also block the natural flow of other proteins important for cellular function. Previous research has used small molecules or enzymes to disrupt these protein aggregates in ameliorating disease. Cyclic peptides offer an alternative to these previous strategies since they affect protein-protein interactions, a process that clearly goes awry in these diseases.
Susan Lindquist and colleagues studied a yeast model system of protein aggregation that shares biochemical features of neurodegenerative disease. They identified several cyclic peptides that rescued disease-induced cell death caused by protein aggregation in yeast. The cyclic peptides also rescued neurons from degeneration in a worm model of neurodegenerative disease. This strategy may be applicable in learning about the mechanism of these diseases and in creating potential treatments.