Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Marco Prado

Abstract

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.


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