The Importance of Down Syndrome Cell Models

Jorge Busciglio, PhD University of California-Irvine

jbuscigl@uci.edu

Questions to be addressed: (1) What is the current state of knowledge of the molecular differences in trisomic cells? (2) How will this knowledge help us develop treatments for people with Down syndrome?

AD pathology in DS

Triplication of the APP gene predisposes individuals with DS to develop AD

A generation

A deposition

Gene expression profile in DS cells: 92 genes differentially expressed

Networks of functionally related proteins in DS cells underscore the presence of mitochondrial dysfunction and oxidative stress in DS --

Beta-Amyloid, Oxidative Stress and Down Syndrome

Current Alzheimer Research, 2006, Vol. 3, No. 5

Mitochondrial dysfunction, oxidative stress and A in DS/AD

Fig. (1). A schematic illustrating the possible links between chromosome 21 gene overexpression and mitochondrial dysfunction. These events in turn may lead to a cascade of damage involving increased oxidative damage, AD pathology and ultimately neuronal dysfunction and cognitive decline in adults with DS. Note that some of these events may feedback and exacerbate the process.

esses in DS: aging and disease development. Factors con-

[5]

Mann DM, Esiri MM. The pattern of acquisition of plaques and

Cellular reprogramming: new disease models and therapeutic potential