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Amyloid Β Peptides, Signalling And Trafficking Of The Α7 Nicotine Receptor, Kirk Young

Electronic Thesis and Dissertation Repository

The α7 nicotinic acetylcholine receptor (nAChR) is an ionotropic receptor for the neurotransmitter acetylcholine and its precursor, choline. Interestingly, α7 nAChR binds amyloid β 42 (Aβ42) peptide, which has a primary role in Alzheimer’s disease pathology. Aβ42 peptide forms aggregates and different structural forms elicit different physiological outcomes. Oligomeric, fibrillar and non-aggregated preparations of Aβ42 were characterized by atomic force microscopy. Immunoblotting of neuronal cells exposed to these preparations determined oligomeric aggregates of Aβ42 mediate ERK1/2 intracellular signalling through α7 nAChR. Cell surface ionotropic receptors are regulated through endocytosis to maintain the integrity of neurotransmission. Cellular pathways for endocytosis of …

Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu

Electronic Thesis and Dissertation Repository

Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.

I found that …