Neurodegenerative disease

Whitehead Institute researchers have determined how the master transcriptional regulator of the heat shock response, known as heat shock factor 1 (HSF1), is controlled in yeast. Understanding how HSF1 works, how it is regulated, and how to fine tune it in a cell-type specific way could lead to therapies for cancer and neurodegenerative diseases.

Prions are infamous for causing Creutzfeld-Jakob disease, fatal familial insomnia, and bovine spongiform encephalopathy, commonly known as mad cow’s disease. Yet, it’s not likely that’s all they’re good for. Using an unbiased screen in yeast, a team of Whitehead Institute and Stanford University scientists have identified dozens of prion-like proteins that could change the defining characteristics of these unusual proteins. 

Whitehead Institute scientists have devised a protocol for pushing human pluripotent stem cells to become microglia—the specialized immune cells that maintain the brain and care for it after injury. Microglia play an important role in neurodegenerative diseases, including Parkinson’s and Alzheimer’s, and studying these cells has been very difficult until now.

Whitehead Institute scientists have determined that a protein known as YOD1 plays a critical role in the disposal of misfolded cellular proteins. The researchers identified YOD1’s role by blocking its function, a manipulation that halts the elimination of errant proteins entirely. The finding should help bring greater understanding to this vital but complex cellular process.