Abstract
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The use of induced pluripotent stem cells (iPSCs), whereby a patient’s
somatic cells can be reprogrammed to a pluripotent state by the forced
expression of a defined set of transcription factors, has the potential
to enable in vitro disease modelling and be used for drug discovery
programs. Alzheimer’s disease (AD) is a progressive neurodegenerative
brain disorder that leads to a decline in memory and cognition. Fibroblasts
were taken from AD patients (or non-AD controls) and cultured under
specific conditions to generate iPSCs which were then provided with
growth factors to allow differentiation into neurons. While AD-iPSCs
were morphologically indistinguishable from control-iPSCs, differentiated
cells showed differing responses to cellular stresses. Since these cells
are derived from individual patients, the use of iPSCs have provided
novel insights into disease pathogenesis, providing information on an
individual’s variations in the disease process and their cellular response
to drugs. Using this system we have identified a number of drugs that
protect AD neurons against the damaging effects of oxidative stress.