Tuesday, September 30, 2014 4:19:20 PM
Abstract Number: 284-LB
Title: A Calcium-dependent Protease As a Potential Therapeutic Target for Wolfram Syndrome, a Prototype of Endoplasmic Reticulum–associated Diabetes
Presentation Start: 6/15/2014 12:00:00 PM
Presentation End: 6/15/2014 2:00:00 PM
Authors: SIMIN LU, KOHSUKE KANEKURA, CHRISTINE M. OSLOWSKI, RITA MARTINEZ, MAYU YAMAZAKI-INOUE, MASASHI TOYODA, AMBER NEILSON, PATRICK BLANNER, CRIS BROWN, JONATHON WASSON, BESS A. MARSHALL, TAMARA HERSHEY, AKIHIRO UMEZAWA, PETER A. GREER, FUMIHIKO URANO, St. Louis, MO, Boston, MA, Tokyo, Japan, Kingston, ON, Canada
Abstract: Endoplasmic reticulum (ER) is an emerging target for human chronic diseases, and Wolfram syndrome characterized by diabetes and neurodegeneration is a prototype of human ER disease. Here we show that the calpain protease is a link between the two Wolfram syndrome genes and death of neurons and ß cells. Calpain activation is mediated by calcium leakage from the ER, which is enhanced by the loss of function of the Wolfram syndrome 1 gene. We show that the Wolfram syndrome 2 gene product (WFS2) associates with and regulates calpain 2. Elevated activation of calpain 2, seen with WFS2 knockdown, correlates with increased death in neurons and ß cells; whereas suppression of calpain 2, seen with over-expression of WFS2, protects these cells from death. Evidence of calpain hyperactivity is observed in a mouse model of Wolfram syndrome as well as in neural progenitor cells derived from induced pluripotent stem cells of patients with Wolfram syndrome. Our results demonstrate that the pathway leading to calpain 2 activation provides potential therapeutic targets for Wolfram syndrome and other ER-associated diseases.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=104383799
You may want to re read my stickie. note, " and other ER associated diseases "
Ambs does not own Calpain 2
There is a large body of literature on this subject. I did not select particular articles, since I am sure that you are more than qualified to select the correct articles on your own.
http://scholar.google.com/scholar?q=calpain+2+inhibitor&hl=en&as_sdt=0&as_vis=1&oi=scholart&sa=X&ei=mRArVPrLDtSnyAS18oLwBg&ved=0CDEQgQMwAA
The truth is incontrovertible. Malice may attack it, ignorance may deride it, but in the end, there it is.
Winston Churchill
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