Mechanisms of neuroprotection against ischemic insult by stress-inducible phosphoprotein-1

Author

Jason Xu, The University of Western OntarioFollow

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Marco Prado

2nd Supervisor

Dr. Vania Prado

Joint Supervisor

Abstract

Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrP^C) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrP^C, α7nAChR, and ALK2 prior to oxygen-glucose deprivation (OGD). STI1 treatment significantly decreased apoptosis and cell death in neurons submitted to OGD in a manner dependent on PrP^C, α7nAChR, and ALK2. Activation of both the α7nAChR and ALK2 receptor were effective at decreasing neuronal death in response to ischemia, suggesting that α7nAChR and ALK2 receptor may be novel targets for preventing death of neurons after ischemia.

Recommended Citation

Xu, Jason, "Mechanisms of neuroprotection against ischemic insult by stress-inducible phosphoprotein-1" (2015). Electronic Thesis and Dissertation Repository. 3463.
https://ir.lib.uwo.ca/etd/3463