Increased Sirt1 expression protects against neurodegeneration in HD mouse model

June 18, 2017

The MGH-MIND team also discovered a new target for Sirt1 activity in TORC1, a brain protein known to regulate several important neuronal genes, and found that the presence of mutant huntingtin interferes with the interaction between Sirt1 and TORC1, reducing expression of the regulated genes. In the same issue of Nature Medicine, a research team based at Johns Hopkins School of Medicine reports similar neuroprotective effects for Sirt1. Co-authored by members of Krainc's team, the Hopkins study demonstrated that mutant huntingtin inhibits the activity of Sirt1, leading to deregulation of multiple Sirt1 targets, in two additional HD mouse models.

"Development of therapeutic agents for neurodegenerative diseases requires an in-depth understanding of the mechanisms that link the underlying biology with the resulting neuronal dysfunction," says Krainc, an associate professor of Neurology at Harvard Medical School. "Developing and testing Sirt1 activators that protect against disorders like HD will require accurate information on Sirt1 activity in the normal and diseased brain. We hope our studies can contribute valuable data to that effort, which will require collaborations with NIH, with industry and with foundations such as the Cure Huntington's Disease Initiative, one of the supporters of this study."

Source: Massachusetts General Hospital