From Dr. Urano's blog today "Instead of directl

From Dr. Urano's blog today

"Instead of directly targeting calpain 2, we are looking for a way to control the upstream event leading to calpain 2 activation. The upstream event is the dysregulation of cellular calcium homeostasis. I will keep you updated about our progress."

http://wolframsyndrome.dom.wustl.edu/a-discov...-syndrome/

From Amarantus and Washingon University Sponsored Research Agreement

"Aim 2. To test if MANF can confer protection against ER dysfunction-mediated cell death using retinal pigment epithelial cells and retinal ganglion cells derived from Wolfram syndrome iPS cells.

We have recently reported that the loss of function of WFS1 causes the leakage of calcium from the ER to the cytosol and subsequent calpain 2 activation, leading to cell death. We will test if MANF can prevent calpain 2-mediated cell death.

Retinal pigment epithelial cells and retinal ganglion cells derived from control and Wolfram syndrome iPS cells will be pretreated with different concentrations of MANF for 24 h, and then challenged with or without an ER stress-inducer thapsigargin (0.5 mM) for another 24 h. Calpain 2 activation and cell death will be monitored by spectrin cleavage and caspase 3 cleavage respectively. We will also isolate RNA from these cells and study the gene expression profiles to identify survival genes activated by MANF in retinal pigment cells and retinal ganglion cells."

http://www.sec.gov/Archives/edgar/data/142481...ex10-1.htm


"Increase in concentration of calcium in the cell results in calpain activation, which leads to unregulated proteolysis of both target and non-target proteins and consequent irreversible tissue damage."

http://en.wikipedia.org/wiki/Calpain


Until they figure out how to control the upstream, will be interesting to find out if MANF protects cells as a result of calpain 2 activation.