Translational research and development of selective nucleotide kinase inhibitors for therapy of Alzheimer disease

Alzheimer disease (AD) is a progressive brain disorder that damages and eventually destroys brain cells, leading to a loss of memory, thinking and other brain functions. Currently, AD is one of the major cause of death in developed countries and the only one of the top ten without a means to prevent, cure or significantly slow its progression. Therefore, the new therapeutic concepts are urgently needed to improve survival and quality of life for AD patients and families. Our previous work resulted in identification of novel selective nucleoside based inhibitors of MARK4 kinase, which has been implicated in development of AD pathology. Here we propose complex translational research leading to synthesis and validation of biological activities of MARK4 inhibitors under both in vitro and in vivo conditions using animal and human models of AD and identification of preclinical candidates for anti-Alzheimer drugs.