Stress Induced Protein 1 (STI1) protects neurons against Beta-Amyloid (Abeta) neurotoxicity

Author

Amro Hasan Mohammad, The University of Western OntarioFollow

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Marco Prado

Abstract

The glycosylphosphatidylinositol (GPI)-anchored Prion Protein (PrP^C) is known for mediating neurotrophic actions after binding to the Stress Induced Protein 1 (STI1). STI1 induces neuronal survival through Ca²⁺ influx via the PrP^C-alpha 7 nicotinic acetylcholine receptor (α7nAChR) complex. Recently, PrP^C 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 PrP^C-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 PrP^C and α7nAChR dependent way. Aβ-induced neuronal death was dependent on the presence of PrP^C. STI1 rescued neurons against Aβ-induced neurotoxicity. Results indicate that STI1 can protect against Aβ, possibly through the PrP^C-α7nAChR complex.

Recommended Citation

Mohammad, Amro Hasan, "Stress Induced Protein 1 (STI1) protects neurons against Beta-Amyloid (Abeta) neurotoxicity" (2012). Electronic Thesis and Dissertation Repository. 858.
https://ir.lib.uwo.ca/etd/858