We have discovered the mechanisms of cell death under ER stress conditions. A key molecule involved in this process is called TXNIP. Expression of this molecule is increased in cells from WFS1 knockout mice, a mouse model of Wolfram syndrome. TXNIP has been shown to play a role in the initiation of inflammation. Although Wolfram syndrome is not an autoimmune disease, I think that "local" iflammation may be involved in the pathogenesis or TXNIP may activate unknown cell death pathways under ER stress conditions. Interestingly, calcium plays a role in the activation of this molecule. We recently found another enzyme which plays a role in calcium-mediated cell death in Wolfram syndrome. I feel that TXNIP or calcium homeostasis is a good drug target for Wolfram syndrome. Our article has been selected for the featured article in Cell press. So you can read it for free. You can also read a preview for our article. A press release from Washington University is informative. JDRF also did a press release for us.
http://www.cell.com/cell-metabolism/home
https://news.wustl.edu/news/Pages/24091.aspx
http://www.jdrf.org/index.cfm?page_id=117576
