Challenging cognition: The DYRK1A gene over-expression seen in Down syndrome causes learning defects and experimental treatments may reduce protein allowing for normal learning capability

The purpose of this thesis is to investigate the cause of cognitive defects and motor abnormalities displayed in Down syndrome individuals. Down syndrome (DS) is the most common genetic defect correlated with mental retardation, delayed development, and cognitive and learning deficits. Increased expression of the dual-specificity gene DYRK1A, which is highly conserved throughout evolution, appears to play a significant role in the neuropathology of DS. In addition, there is a higher incidence of certain autoimmune disorders associated with extra material on chromosome 21; however, the extra material has been linked to have a protective effect against (MS) Multiple Sclerosis and certain cancers (Weilback & Toyka, 2002).;The human gene DYRK1A is located in the Down syndrome critical region (DSCR) 21q22.2 (Antonarakis, 1991). DYRK1A is translocated into the nucleus and involved in the control of cell growth and development. This gene has unique genetic and biochemical properties, which plays a role in proliferation of neural progenitor cells and neuronal differentiation (Galceran et al., 2004; Kay, 2009; Mobley, 2009). An increased gene dosage of human DYRK1A in trisomy 21 disrupts the function of fully differentiated neurons, and this disruption may be reversible (Kay, 2009, Mobley, 2009).;With the development of modern molecular technologies and the mapping of the human genome, Stanford Center for Down syndrome and genetics research is in the process of studying the idea whether the gene can be turned off or its expression of its protein reduced. To explore this hypothesis, this experiment was conducted with transgenic mice that have an over-expression of DYRK1A. In Barcelona, Spain, these adult mice were given an injection of adeno-associated virus type 2, which normalized the DYRK1A protein levels. More importantly, the mice reduced their hyperactive behavior, restored motor abnormalities, and improved their cognitive ability. Therefore, the data suggest that normalizing DYRK1A gene expression in the adult TgDYRK1A mice, clearly makes this a potential therapy in Down syndrome in the future (Abalia et al., 2008). Only then can we imagine the beneficial impact on the lives of affected individuals with Down syndrome.