This thesis work describes the role of Rab proteins in amyloid processing and clearance in different cell pathways. It also describes an experimental approach used to analyze the expression effects of Rab10 in amyloid beta production. Since the main theory behind neurodegeneration in Alzheimer's disease claims that high levels of amyloid beta 42 (Aβ42) molecules trigger widespread neuronal death, control of Aβ42 has been a main target in Alzheimer's disease research. In addition, several studies show increased levels of particular Rab proteins in Alzheimer's pathogenesis. However, no review consolidates current findings in neurodegeneration of Alzheimer's with Rab protein dysfunction. The first chapter of this thesis aims to address this need by providing a current review of Rab proteins associated with APP and neurodegeneration. The second chapter constitutes an experimental approach used to characterize the effects of Rab10 and Sar1A GTPases in APP and amyloid processing. We found that Rab10 expression does not affect APP production but significantly changes Aβ generation, particularly the toxic Aβ42 and Aβ42:40 ratio. On the other hand, we found no significant effect of Sar1A expression on either APP or amyloid beta generation. These findings partially confirm the work done by Kauwe et al (2015) and provide preliminary evidence for two potential targets for protective effects in neurodegeneration.
College and Department
Life Sciences; Biology
BYU ScholarsArchive Citation
Arano Rodriguez, Ivan, "Rab Proteins and Alzheimer's: A Current Review of Their Involvement in Amyloid Beta Generation with Focus on Rab10 Expression in N2A-695 Cells" (2015). All Theses and Dissertations. 5648.
Rab proteins, GTPases, Alzheimer's disease, gene, genetic variants, 3' UTR, amyloid beta, neurodegeneration, endocytosis, anterograde transport, autophagy, amyloid precursor protein, transient transfection, overexpression, knockdown