Association of Hirano bodies and C31 fragment of the amyloid precursor protein
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Hirano bodies are cellular inclusions found in patients suffering from neurodegenerative diseases. However, the physiological function of Hirano bodies is not understood. A previous study shows that Hirano bodies sequester and protect against AICD, the C58 fragment of the amyloid precursor protein (APP) (Ha, et al., 2009). Due to the observed association between Hirano bodies and Alzheimer’s disease, we investigated the relationship between Hirano bodies and the neurotoxic effects of the C31 fragment of APP, a fragment that has been suggested to be more lethal than AICD. APP can be intracellularly cleaved by caspases at the C-terminus to produce C31. Furthermore, studies have indicated that a mutation from aspartic acid to alanine at amino acid 664 alters the caspase cleavage site leading to a decrease in both amyloid-β and C31 toxicity (Lu, et al., 2003). Experiments were conducted in wild-type (WT) human embryonic kidney (HEK) 293 cells or CT cells, cells expressing Hirano bodies. Cells were transfected with either the C31 fragment tagged with myc or a C31 fragment with a mutation from NPTY to NATA (mC31). The viability of cells with Hirano bodies expressing either C31 or mC31 was compared. Different oncentrations of C31 and mC31 were used to see if cell death was concentration dependent. Finally, immunofluorescence microscopy was used to see where C31 was found or if C31 co-localized with Hirano bodies.