Master of Science
Anatomy and Cell Biology
Dr. Marco Prado
The glycosylphosphatidylinositol (GPI)-anchored Prion Protein (PrPC) is known for mediating neurotrophic actions after binding to the Stress Induced Protein 1 (STI1). STI1 induces neuronal survival through Ca2+ influx via the PrPC-alpha 7 nicotinic acetylcholine receptor (α7nAChR) complex. Recently, PrPC was found to be a receptor for beta-amyloid oligomers (Aβ) and a mediator of Aβ neurotoxicity. We hypothesized that STI1 promotes neuronal survival against the neurotoxicity of Aβ. A Ca2+ signaling assay was used to test the STI1 and Aβ dependence on the PrPC-α7nAChR complex for Ca2+ influx. Cell death assays were performed to assess the STI1 ability to protect against Aβ-induced neurotoxicity on embryonic hippocampal neurons. Aβ induced sustained Ca2+ influx in a PrPC and α7nAChR dependent way. Aβ-induced neuronal death was dependent on the presence of PrPC. STI1 rescued neurons against Aβ-induced neurotoxicity. Results indicate that STI1 can protect against Aβ, possibly through the PrPC-α7nAChR complex.
Mohammad, Amro Hasan, "Stress Induced Protein 1 (STI1) protects neurons against Beta-Amyloid (Abeta) neurotoxicity" (2012). University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 858.