Overall, we demonstrated that CBS overdosage underpins the DS-related recognition memory deficit and that both CBS and DYRK1A interact to control accurate memory processes in DS.
We here demonstrate that pharmacological inhibition of brain DYRK1A is able to correct recognition memory deficits in three DS mouse models with increasing genetic complexity [Tg(<i>Dyrk1a</i>), Ts65Dn, Dp1Yey], all expressing an extra copy of <i>Dyrk1a</i> Overexpressed DYRK1A accumulates in the cytoplasm and at the synapse.
Overexpression of the Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) gene contributes to the retardation, craniofacial anomalies, cognitive impairment, and learning and memory deficits associated with Down Syndrome (DS).
Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains.
Nonchimeric polytransgenic 152F7 mice encompassing four human chromosome 21 genes (DSCR3, DSCR5, TTC3, and DYRK1A) within the Down syndrome critical region present with learning and memory impairment.
These mice represent the most clinically relevant DYRK1A mouse model to date and provide us a valuable tool for the in vivo study of mechanisms that underlie the learning and memory deficit in DS.