Novel DYRK1A Inhibitor Rescues Learning and Memory Deficits in a Mouse Model of Down Syndrome
Wenche Stensen, Ulli Rothweiler, Richard A. Engh, Melissa R. Stasko, Ilya Bederman, Alberto C. S. Costa, Anders Fugelli, John S. Svendsen
Abstract
Down syndrome (DS) is a complex genetic disorder associated with substantial physical, cognitive, and behavioral challenges. Due to better treatment options for the physical co-morbidities of DS, the life expectancy of individuals with DS is beginning to approach that of the general population. However, the cognitive deficits seen in individuals with DS still cannot be addressed pharmacologically. In young individuals with DS, the level of intellectual disability varies from mild to severe, but cognitive ability generally decreases with increasing age, and all individuals with DS have early onset Alzheimer's disease (AD) pathology by the age of 40. The present study introduces a novel inhibitor for the protein kinase DYRK1A, a key controlling kinase whose encoding gene is located on chromosome 21. The novel inhibitor is well characterized for use in mouse models and thus represents a valuable tool compound for further DYRK1A research.