Alzheimer's Disease Model Cells Derived from Human iPS Cells
Poster Mar 20, 2015
Honda M; Kitogo T; Kogami H; Inamura M
Alzheimer's disease (AD) is the most common cause of dementia characterized by impaired memory and cognitive dysfunction due to neurodegeneration. The predicted increase in AD morbidity coupled with the socioeconomic impact of the disease has necessitated the urgent development of an effective therapy. However, the currently available models of AD are challenging and a more humanized, scalable assay system is required to better understand the disease and identify novel therapies.
There are two methods to develop AD model cells based on human induced pluripotent (iPS) cells. The first method uses targeted genetic modification of human iPS cells, and the other involves the production of human iPS cells from patients with AD. We supply both types of AD model cells depending on request.
In this poster, we describe how we developed the AD model cells (ReproNeuro Ach-ADTM and ReproNeuro Glu-ADTM ) by generating human iPS cells containing a mutant Presenilin 1 (PS1) gene, which is responsible for familial AD, and differentiating these cells into cholinergic neurons or glutamatergic neurons. In the brains of patients with AD, cholinergic neurons are damaged and the glutamate system is disrupted. To confirm whether these neurons can be used for drug screening, we performed characterization of these neurons as well as the Aβ assay. The effect of these neurons on the production of Aβ40 and Aβ42 was measured using the AlphaLISA® Human Amyloid β1-40/1-42 immunoassay kit (Perkin-Elmer) for high-throughputscreening (HTS).
The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of phase I (cytochrome P450s), phase II metabolizing enzymes and transporter genes in response to xenobiotics, including prescription drugs.READ MORE