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Role of the proliferation-related molecules in the pathogenesis of Alzheimer’s Disease

Yates, Sharon Christine (2012)
M.Phil. thesis, University of Birmingham.

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Abstract

The cell cycle theory of Alzheimer’s Disease (AD) states that neurodegeneration is secondary to aberrant cell cycle activity in neurons. Previous studies suggest that this may be partly attributed to alterations in the mTOR pathway, which promotes cell growth and division, and partly to genetic variants on genes responsible for cell cycle control.

In this study we perform a systematic analysis of the rapamycin-regulated genes that are differentially regulated in brain affected by AD compared to control. These genes may serve as novel therapeutic targets or biomarkers of AD. Secondly, we investigate the association of a cancer-associated variant of p21$$^{cip1}$$, and a variant of p57$$^{kip2}$$, with AD. These cyclin dependent kinase inhibitors are crucial cell cycle regulatory components that function downstream of mTOR. We confirm the association of the p21$$^{cip1}$$ SNPs with AD, and inform on the mechanisms by which they cause loss of function. We also show a weak association between variant p57$$^{kip2}$$ and AD. Furthermore, we demonstrate that p57$$^{kip2}$$ is differentially imprinted in the frontal and occipital lobe; and suggest that AD may be associated with change in the imprinting status of p57$$^{kip2}$$ in the brain.

Type of Work: M.Phil. thesis. Bicknell, Roy and Nagy, Zsuzsanna Colleges (2008 onwards) > College of Medical & Dental Sciences School of Immunity and Infection QH301 BiologyRC0321 Neuroscience. Biological psychiatry. Neuropsychiatry University of Birmingham 3648
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